",isbn:"978-1-80356-966-6",printIsbn:"978-1-80356-965-9",pdfIsbn:"978-1-80356-967-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"f86a9f720cc3ac0f1c385d0367ea89b9",bookSignature:"Dr. Fiaz Ahmad and Prof. Muhammad Sultan",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11624.jpg",keywords:"Agricultural Waste, Reuse, Reduction, Soil Health, Recycling, Agriculture and Environment, Modelling and Simulation, Agro-Industrial Waste, Bioresource Processing, Processing and Management, Crop Residue, Forest Waste",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 8th 2022",dateEndSecondStepPublish:"June 16th 2022",dateEndThirdStepPublish:"August 15th 2022",dateEndFourthStepPublish:"November 3rd 2022",dateEndFifthStepPublish:"January 2nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"17 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Fiaz Ahmad is a researcher in the field of Agricultural Engineering with fifteen years of field and academic experience, currently in charge of the Agricultural Machinery Design Laboratory at Bahauddin Zakariya University. He applied for two patents at the national level.",coeditorOneBiosketch:"A renowned researcher in the field of Agricultural Engineering with 14 years of academic experience at Bahauddin Zakariya University. Winner of various prestigious fellowships, awards, and research grants. Published 250+ articles along with several books and chapters. Guest editor of seven ISI-SCI journals for publishers like SAGE, MDPI, and Frontiers.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"338219",title:"Dr.",name:"Fiaz",middleName:null,surname:"Ahmad",slug:"fiaz-ahmad",fullName:"Fiaz Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/338219/images/system/338219.png",biography:"Dr. Fiaz Ahmad is an assistant professor and lecturer at the Department of Agricultural Engineering, Bahauddin Zakariya University, Multan, Pakistan. He obtained his Ph.D. in Agricultural Bioenvironmental and Energy Engineering from Nanjing Agriculture University, China, in 2015, and completed his postdoctorate in Agricultural Engineering from Jiangsu University, Zhenjiang, China, in 2020. He was awarded a fellowship from the Higher Education Commission of Pakistan for Ph.D. studies and from the Chinese Government for post-doctoral studies. He earned a BSc and MSc (Hons) in Agricultural Engineering from the University of Agriculture, Faisalabad, Pakistan, in 2004 and 2007, respectively. He is the author of more than fifty journal and conference articles. He has supervised six master’s students to date, and is currently supervising six master and two doctoral students. Dr. Ahmad has completed three research projects with his research interest focusing on the design of agricultural machinery, agricultural waste management, artificial intelligence (AI), and agricultural bioenvironment.",institutionString:"Bahauddin Zakariya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Bahauddin Zakariya University",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:{id:"199381",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sultan",slug:"muhammad-sultan",fullName:"Muhammad Sultan",profilePictureURL:"https://mts.intechopen.com/storage/users/199381/images/system/199381.png",biography:"Muhammad Sultan is an Assistant Professor at the Department of Agricultural\r\nEngineering, Bahauddin Zakariya University, Multan (Pakistan). He completed his Ph.D.\r\nand Postdoc from Kyushu University (Japan) in the field of Energy & Environmental\r\nEngineering. He was an awardee of MEXT and JASSO fellowships (from the Japanese\r\nGovernment) during Ph.D. and Postdoc studies, respectively. He also did a Postdoc as\r\na Canadian Queen Elizabeth Advance Scholar at Simon Fraser University (Canada) in\r\nthe field of Mechatronic Systems Engineering. He worked for Kyushu University\r\nInternational Institute for Carbon-Neutral Energy Research (WPI-I2CNER) for two years.\r\nCurrently, he is working on 4 research projects funded by the Higher Education\r\nCommission (HEC) of Pakistan. He has completed six projects in past in the field of\r\nagricultural engineering. He has supervised 10+ M.Eng. and Ph.D. thesis and 10+\r\nstudents are currently working under his supervision. He has published 120+ journal\r\narticles, 100+ conference articles, 13 book chapters, and 6 books. He is serving as guest\r\neditor for the journals like Sustainability (MDPI), Agriculture (MDPI), Energies (MDPI),\r\nAdvances in Mechanical Engineering (SAGE), Frontiers in Mechanical Engineering, and\r\nEvergreen Journal of Kyushu University. His research is focused on developing energy-\r\nefficient temperature and humidity control systems for agricultural storage, greenhouse,\r\nlivestock, and poultry applications. His research keywords include desiccant air-\r\nconditioning, evaporative cooling, adsorption heat pump, Maisotsenko cycle (M-cycle),\r\nenergy recovery ventilators; adsorption desalination; wastewater treatment.",institutionString:"Bahauddin Zakariya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Bahauddin Zakariya University",institutionURL:null,country:{name:"Pakistan"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"440212",firstName:"Elena",lastName:"Vracaric",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/440212/images/20007_n.jpg",email:"elena@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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1. Introduction
The term “Glaucoma” integrates a wide range of eye diseases characterized by a diversity of clinical forms: mainly by the chronic course and rather unfavourable prognosis. Sufficient to mention that in developed countries the frequency of vision loss due to glaucoma is steadily at the level of 15-20% of the total number of all blind subjects [Nesterov A.P., 2008].
It is considered long-established that among various clinical-and-anatomical manifestations of the glaucomatous process the anterior open-angle glaucoma is the most frequently diagnosed form.
The severity of course of anterior open-angle glaucoma and especially the unfavourable outcomes of the disease are mainly connected with those unsolvable problems faced by ophthalmologists at the study of pathogenesis of primary and secondary glaucomas. Precisely this circumstance is the “insurmountable” obstacle in pathogenetic therapy, thus limiting the entire complex of medical interventions within the early symptomatic therapy with underlying local application of hypotensive means aimed to decrease intraocular pressure.
To a known extent, the interpretation of aspects of pathogenesis in case of anterior open-angle glaucoma is connected to the fact that this type of glaucoma is rather frequently associated with the cataract and pseudoexfoliative syndrome.
At present the etiopathogenetic links engaged in induction and the course of anterior open-angle glaucoma are conditionally divided into general and local ones.
Heredity, general type changes in specific integrative systems of the organism (CNS, endocrine, immune and cardiovascular) are among the general factors bringing forth disorders of the hematoophthalmic barrier and the increase of intraocular pressure.
Amongst the local factors relatively persistent elevation of intraocular pressure, primary dystrophic and atrophic changes, including age-related shifts in the cornea, ciliary body and the trabecular meshwork, which cause the infringement of hydrodynamic and hydrostatic properties of the aqueous humour, are considered.
As mentioned by A.P. Nesterov (2008) chronologically occurring processes, which might be conditionally subdivided into 2 stages, are engaged in the pathogenesis of glaucomas in anterior and posterior chambers of an eye. At the first stage mechanisms bringing forth the increase of intraocular pressure are triggered in the anterior chamber of an eye. At the second stage mechanisms localized in the posterior part of the eye chamber are initiated and in the long run become the cause of atrophy of the visual nerve. At that, the “glaucomatous process” firstly originates in the anterior chamber of an eye, while the dystrophic and atrophic processes in the visual nerve are resulting from the exposure to high intraocular pressure.
During the last years, rather informative evidences were obtained to discuss the role of biologically active substances produced in situ, i.e. in specific eye membranes, in mechanisms of anterior open-angle glaucoma origination using the clinical and experimental material.
We did not set the problem to analyze the current state of the art on the role of general pathogenetic factors engaged in induction and the course of anterior open-angle glaucoma.
The currently available data of scientific publications and results of our own investigations devoted to the role of in situ produced biologically active substances of cytokine, mediatory and hormonal origin in mechanisms of a stable increase of the intraocular pressure in case of anterior open-angle glaucoma will be analyzed in this work.
2. Secretory-mediatory hormone-dependent functions of eye membranes in the mechanisms of glaucoma development
2.1. The role of transforming growth factor β-2 (TgFβ-2), insulin-like growth factor-1 (IgF-1) and Е2 prostaglandins (PgE2) in pathogenesis of primary open-angle glaucoma
Nowadays the role of TGFβ produced in post-barrier membranes of an eye is considered to be of no less importance for realization of processes ensuring the drainage function of the eye anterior chamber-associated immune deviation (ACAID) [Mansfield K. et al., 2004; Banh A. et al., 2006; Kim Y.S. et al., 2008; Dawes L.J. et al., 2009]. According to scientific publications, TGFβ-2 produced in the post-barrier membrane of an eye (in cornea, ciliary body, retina) at some eye diseases takes an active part in the increase of intraocular pressure [de Iongh R.U. et al., 2005; Stefan C. et al., 2008; Dawes L.J. et al., 2009; Hindman H.B. et al., 2010; Pattabiraman P.P, Rao P.V., 2010].
To our mind, during the last years rather informative data signifying in favour of pleotropic potencies of TGFβ-2 produced in post-barrier membranes of the eye.
In particular, in a post-surgery period in patients operated for complicated and senile cataracts in situ produced TGFβ-2 induces trans-differentiation of epithelial cells of crystalline lens capsule into fibroblasts; this latter was manifested as opacity of lens with all the subsequent after-effects [Dawes L.J. et al., 2009]. The modulatory effect of TGFβ-1 towards the processes of activation of cells of fibroblastic line in the cornea was also established. Thus, the authors [Karamichos D. et al., 2010] under conditions of cultivating cells of cornea using TGFβ-1 dose-dependent mode activated in situ synthetic processes in fibroblasts, thus bringing forth intensification of collagen(ous) fibrilles synthesis and eventually to regional overgrowth of immature connective tissue with the resulting fibrosis.
TGFβ-2 high level was also revealed in cells of the trabecular meshwork of patients with open-angle glaucoma [Stefan C. et al., 2008]. The authors consider that at the mentioned disease TGFβ-2 stimulates fibronectin synthesis in trabecular cells, thus predefining “profibrotic” effects of TGFβ-2 in post-barrier membranes of the eye.
Literature data is available [Ochiai Y., Ochiai H., 2002], according to which in patients with anterior open-angle glaucoma, diabetes complicated by anterior open-angle glaucoma the level of TGFβ-2 in aqueous / intraocular humor is markedly increased. As a control, the authors studied aqueous humour of patients with cataracts.
Processes reflecting the specific precise stages of TGFβ-2 and IGF-1 activity in post-barrier membranes of the eye are the subject of a wide discussion. Furthermore, the study on mechanisms of their direct and/or mediated interaction in processes ensuring the drainage function of an eye is mainly emphasized.
In the organism of mammals, the post-barrier membranes of an eye also serve as a source of both cytocines. IGF-1 and its receptors, IGF-IR, were found in epitheliocytes of lens and cornea, epitheliocytes of retina meshwork, Muller\'s cells [Shaw L.C. et al., 2006; Ko J.A. et al., 2009]. TGFβ-2 is produced in post-barrier membranes of an eye and, first of all, in fibroblasts of cornea [Streilein J. et al., 1992; Wilkbanks G. et al., 1992; Hollborn M. et al., 2000; Fleenor D. et al., 2006].
According to C. Stefan et al. (2008), cells of the trabecular meshwork of the anterior angle of the eye chamber might serve as the source of TGFβ-2 synthesis.
S.H. Chung and associates used human lens epithelial cells (HLE B-3) to reveal the role of IGF-1 in processes of TGFβ-2 mediated fibronectin accumulation in lens cells [Chung S.H. et al., 2007]. Based on analysis performed by the authors (reverse polymerase transcriptase chain reaction, immune-fluorescent studies) mentioned researchers draw a conclusion that IGF-1 counteracts TGFβ-2 induced fibronectin accumulation in lens epitheliocytes.
J.A. Ko et al. (2009) studied the role of IGF-1 in intrercellular regulation in cultured fibroblasts and human corneal epitheliocytes. According to authors, the presence of epitheliocytes in the culture medium enhanced N-cadherin expression in fibroblasts. Similar effect of corneal epitheliocytes was also simulated by IGF-1, but not fibroblasts growth factor or epidermal growth factor. The authors conclude that IGF-1 produced in epitheliocytes regulates N-cadherin positive expression in corneal fibroblasts.
There is an opinion that IGF-1 and IGF-2 regulate the processes of proliferation and apoptosis in corneal epitheliocytes [Yanai R. et al., 2006]. According to K. Izumi and co-workers (2006), TGFβ produces an influence to corneal fibroblasts differentiation into myofibroblasts. Moreover, IGF-1 is engaged in this mechanism. Thus, treatment with TGFβ-2 caused expression of IGF-1, mRNA, IGF ВР-3 and IGF ВR-3 protein in human corneal. According to N. Yamada et al. (2005), IGF-1, alongside with fibronectin, IL-6 and substance P, actively participate in stimulation of fibroblastic processes in cornea.
The analysis of above mentioned scientific publications signifies to the important role of in situ produced TGFβ-2 and IGF-1 in mechanisms of fibroblastic processes formation and their cellular metaplasia in specific eye membranes: in post-barrier eye membranes in ACAID mechanisms and withdrawal. One cannot exclude that locally produced cytokines possess short-distant range of activity; moreover, their realization might occur according to either the principles of intercellular interaction, i.e. through the paracrine mechanism, or on the basis of intercellular autocrine regulation. Apparently, both mechanisms have an important part in infringement of drainage function of an eye at different types of glaucoma.
As known, prostaglandins play an important role in integrative activity of the mammalian organism, in particular, in regulation of immunogenesis, hemostasis, non-specific resistance at the organism level [Kuznik B. et al., 1989].
However, until present the probability of prostaglandins synthesis in post-barrier membranes of an eye seems still disputable.
There are only sporadic communications related to the mentioned aspect; an attempt was made to reveal Е1, Е2 and F2α prostaglandins in post-barrier membranes of an eye and in the aqueous humour.
It is considered established that prostaglandins increase intraocular pressure and infringe the function of hematoophthalmic barrier [Podos S.M. et al., 1972 a; b; Podos S.M., 1976a ; b; c]. Moreover, the drainage function of an eye is simultaneously realized by prostaglandins in the aqueous humour.
According to C.B. Toris and associates, numerous prostaglandin-dependent effects in post-barrier membranes of an eye are realized according to the receptor mechanism associated at the level of mRNAs [Toris C.B. et al., 2008]. Similar receptors were revealed in the trabecular meshwork, celiar muscle, and sclera.
Prostaglandin-dependent receptors in post-barrier eye membranes were revealed not only in humans, but also in rats, mice, rabbits, pigs and monkeys. Considering the vasoactive properties of prostaglandins, as well as their role in sustaining the drainage function of an eye, the sysnthetic analogs of prostaglandins are widely applied in ophthalmological practice for treatment of glaucoma [Bucci F.A., Waterbury L.D., 2008; Toris C.B. et al., 2008].
Therefore, it is no excluded that Е2 prostaglandins might participate in maintenance of the drainage function and, appropriately, the intraocular pressure as well; similar mechanisms of prostaglandins functioning in post-barrier membranes of the eye are realized exceptionally according to the receptor mechanism.
Taking into account the abovementioned, an assumption might be proposed according to which in situ produced Е2 prostaglandins are engaged into the pathological process observed at the area of post-barrier membranes of an eye at primary open-angle glaucoma.
2.2. The role of fibronectin in pathogenesis of primary open-angle glaucoma
Fibronectins are a group of cold-insoluble glycoproteids with the molecular mass 400.000–450.000 D localized both on the surface of connective tissue cells and in the extracellular matrix. The following functionally active domains were revealed in fibronectin structure: NH2 terminal domain includes sites of fibrin binding; then collagen and heparin binding domains and domain ensuring cells adhesion are localized; at COOOH-cone there is one more heparin binding domain [Kuznik B. et al., 1989]. Fibronectins have an important part in cells proliferation and differentiation, morphogenesis and embryogenesis of tissues. In particular, tissue fibronectin of fibroblastic genesis actively participates in collagen formation both at norm (at the stage-by-stage process of the connective tissue maturation), and in pathology state (different distrophic and inflammatory processes occurring at the site of the connective tissue. Thus, in particular, an important role is assigned to fibronectin in reparative processes, influence on cells migration, growth and proliferation. Fibronectin produced by cells of the connective tissue (fibroblasts, endotheliocytes, smooth-muscle cells of arterioles, etc.) in its turn actively participates in formation of the extra-cellular matrix, especially at early stages of the connective tissue formation. The following cells of different genesis serve as the main source of fibronectin synthesis: endothelium, hepatocytes, fibroblasts, smooth myocytes, Schwann\'s cells, alveolar and peritoneal macrophages, epitheliocytes, and thrombocytes [Kuznik B. et al., 1989].
Currently the sources of fibronectin synthesis in the post-barrier membranes of an eye are disputable as well. According to H.B. Hindman et al. (2010), corneal keratocytes might be considered as probable sources of fibronectin synthesis. This fact was revealed under cultivation of keratocytes localized in the anterior and posterior parts of cornea. Furthermore, in the process of cultivating corneal cells of fibroblastic line the authors established TGFβ-1-dependent activation of keratocytes, in which a marked activation of fibronectin synthesis occurred. Simultaneously, Thy-1 secretion increases in the same keratocytes. According to D. Karamichos et al. (2010), in situ (in post-barrier membranes of an eye) produced TGFβ-2, under conditions of pathology might serve as a provoking factor binging forth fibrosis of the cornea. Therefore, we cannot exclude that realization of this TGFβ-2 related effect is mediated due to the activation of fibronectin in the same keratocytes.
C. Stefan et al. (2008) use the immune enzyme assay to determine TGFβ-2 and fibronectin concentration in aqueous humour of patients with anterior open-angle glaucoma. The authors revealed a significant increase of TGFβ-2 concentration in this cohort of patients and draw a conclusion that TGFβ-2 produced in post-barrier membranes of the eye should be considered as a “special” cytokine that increases fibronectin concentration in the trabecular meshwork; moreover, it might be considered as a local pro-fibrotic factor.
Sporadic, though rather informative, evidences are available according to which the trabecular meshwork localized in the angle of an anterior chamber of the eye serves as the possible source of fibronectin synthesis. In particular, R.J. Wordinger et al. (2007) studied the probable mechanisms of synthesis of the biologically active substances by trabecular meshwork cells. As known, the cells of trabecular meshwork synthesize and excrete “bone morphogenic protein” – BMP-4. The authors, under conditions of trabecular cells cultivation studied the synthetic potencies thereof at addition of BMP-4 and TGFβ-2 to the culture media. The study results demonstrated that TGFβ-2 treated cells of the trabecular meshwork launched an intense synthesisn of fibronectin, while BMP-4, if additionally introduced to TGFβ-2 containing media, blocked this induction of fibronectin.
Mentioned authors studied the expression of BMP-4 family gens in normal and glaucomatous cells of the trabecular meshwork. Under the influence of these receptors the levels of TGFβ-2 and BMP anatagonist, protein gremlin, significantly increased. The authors succeeded to establish that gremlin blocked the negative impact of BMP-4 towards TGFβ-2 induction of fibronectin.
Another result obtained by the same authors is of no less importance: gremlin introduced in the medium ex vivo, caused the prototype of increased intraocular pressure glaucoma. Research findings of these authors reflect the main statements of the hypothesis according to which in case of the anterior open-angle glaucoma the enhanced expression of gremlin by trabecular meshwork cells inhibits BMP-4 antagonism to TGFβ-2, eventually, might bring forth the increase in deposition of the extracellular matrix and intraocular pressure.
The analysis of rather informative data obtained by mentioned authors allows to draw a conclusion, according to which the trabecular meshwork of an angle of anterior chamber of the eyes should not considered as an object that passively ensures the drainage function thus sustaining optimally stable levels of the intraocular pressure.
To our mind, the drainage function of trabecular meshwork is an active process and the leading role here belongs to “secretory” cells of the meshwork predominantly functioning according to the autocrine mechanism. At dysfunctions of trabecular meshwork cells, especially in case of open-angle glaucoma, the synchronous activity of these cells is infringed; this latter might enhance their specific medatory function – in view of the increased synthesis of fibronectin. Precisely, fibronectin depositions and the subsequent intensification of fibroblastic processes in situ might bring to disorders in drainage function of the trabecular meshwork of the angle of anterior chamber of the eye and, finally to the stable increase of intraocular pressure.
According to D. Fleenor et al. (2006), TGFβ-2 treatment of segments of trabecular meshwork cells of the angle of anterior chamber of the eye resulted in modulation of multiple gens regulating the structure of extracellular matrix. In the trabecular meshwork cells TGFβ-2 brings forth an increased secretion of fibronectin. TGFβ-2 action to cells of the trabecular meshwork was blocked by inhibitors of receptor type 1 TGFβ. In perfusion anterior segments of human eyes TGFβ-2 treatment increased the intraocular pressure and elution of fibronectin. In our opinion the authors come to the rather reasonable conclusion: TGFβ-2 influence on intraocular pressure might be “leveled” by TGFβ-2 -mediated receptors type 1 through prevention of TGFβ-2 stimulating effect to cells of the extracellular matrix.
According to mentioned authors, understanding these inter-mediatory and receptor interactions, which occur at the site of trabecular meshwork of an angle of anterior chamber of the eye, would then allow to develop new efficient approaches for treatment of glaucoma.
There is an opinion [Gonzales J.M. et al., 1998], according to which it is merely domain of heparin II (Hep II) in the structure of fibronectin that regulates the ability outflow (excretory system) in cultured anterior segments through the effects produced to the cytoskeleton in transformed cells of the trabecular meshwork of the angle of the anterior chamber of an eye. The mentioned authors cultivated cells of the trabecular meshwork under conditions of Hep II domain and revealed an active site of this domain that regulates the ability of aqueous humor efflux. According to researchers, precisely this site of a domain is responsible in case of disorders in actinic cytoskeleton of the trabecular meshwork at glaucomas.
Fibronectin concentration in aqueous (intraocular) humour of patients with cataracts and glaucomas, according to K.S. Kim et al. (1992), widely varies from 5 ng/ml to 100 ng/ml (data of immune enzyme assay – ELISA). Authors separated the aqueous humor by aspiration from the eyes of patients with cataract and glaucoma using a special puncture needle introduced through the limbal zone before the limbal incision in the anterior chamber of the eye, that is before the surgical intervention. Due to the performed immune enzyme assay the researchers managed to establish that at glaucomas the level of fibronectin significantly increases compared to its level in aqueous humour of patients with cataracts. At the same time, fibronectin levels in aqueous humor patients with cataract and glaucoma had no dependence on either age or gender of patients under preoperative study.
The aspects related to fibronectin sources in post-barrier membranes of the eye are also discussed. An assumption was made that at primary glaucomas relatively high concentrations of fibronectin accumulate in the anterior chamber of an eye, as it cannot escape the drainage pathways. There are quite opposite data, according to which in patients with the open-angle glaucoma fibrinogen concentration in the aqueous humor significantly did not differ from that of aqueous humor of patients with cataracts [Vesaluoma M. et al., 1998]. At the same time, upon comparison of obtained results of immune enzyme analysis for fibrinogen content on the one hand, in aqueous humor of patients with cataracts and primary glaucomas, and, on the other hand, in patients with exfoliative glaucoma, the level of fibronectin in aqueous humor significantly increased in the latter case. The authors consider that significantly higher concentration of fibronectin in patients with the pseudoexfoliative glaucoma might result from infringement of the hematoophthalmic barrier. There is evidence [Tripathi B.J. et al., 2004] that the growth factor (TGFβ-2) under conditions in vivo modulates fibronectin and stromelysin-1 (MMP-3) in trabecular cells of the anterior chamber of an eye. Mentioned authors studied expression of RNA and fibronectin protein at presence of growth factors in primary and secondary humour of the anterior chamber (taken in pre- and post-operative period, appropriately). In particular, under conditions of incubation of trabecular cells of the anterior chamber of the eye, growth factor containing aqueous humors taken from patients with glaucoma prior to and post the surgery were added to the culture medium. Compare to control, fibronectin mRNA expression by trabecular cells increased by 50 and 100% after incubation in primary samples of aqueous humor during 48 hours or 7 days, as well as by 50 and 160% after incubation in secondary samples of the aqueous humor. MMP-1 mRNA expression decreased by 25 and 50% after incubation in samples of primary aqueous humor during 48 hours or 7 days, as well as by 80 and 85% after incubation during 48 hours or 7 days in secondary samples of aqueous humor. The level of fibronectin increased 3.5 times and 6-fold after incubation during 48 hours with primary and secondary samples of aqueous humor.
Study results obtained by the abovementioned authors allow to draw a conclusion that induction of MMP-3 in the trabecular meshwork of glaucomatous eyes might decrease fibronectin formation in aqueous humor excretion pathways, thus decreasing the resistance of liquid outflow into the anterior chamber of an eye.
The analysis of publications relevant to the role of in situ produced fibronectin in post-barrier membrane of an eye allows to come the following conclusions.
Firstly, the role of in situ produced fibronectin in mechanisms on sustaining the local homeostasis remains debatable.
Secondly, the available scientific literature indicates to the fact that under conditions of norm fibronectin produced by cells of the trabecular meshwork performs the drainage function in outflow of the aqueous humor.
Thirdly, at some eye diseases and especially at primary open-angle glaucoma and pseudoexfoliative syndrome, the excessive synthesis of fibronectin by cells of the trabecular meshwork might bring forth a disorder of the drainage function that eventually in its turn is fraught with the increase of intraocular pressure.
Fourthly, it is not excluded that in post-barrier membranes of the eye there are engaged fibronectin-dependent mechanisms, which function according to both principles of inter-cellular interactions and the autocrine mechanism.
2.3. The role of cortisol in pathogenesis of anterior open-angle glaucoma
At present, aspects related to studies on “endocrine homeostasis” in post-barrier membrane of an eye at both norm and pathology are the subject of a wide discussion in ophthalmology. The available publications are not numerous; furthermore, they are of a rather statement-of-the-fact character [Southren A. et al., 1976; Floman N., Zor U., 1977; Kasavina B. et al., 1977; Weinstein B. et al., 1983; Stone R., Wilson C., 1984; Stojek A. et al., 1991; Chiquet C., Denis P., 2004; Burch J. et al., 2005; Pleyer U. et al., 2005; Schwartz B. et al., 2005; Vessey K. et al., 2005]. In particular, there are reports discussing the possibility of cortisol local synthesis in eye membranes.
The autopsy material (vitreous body and blood serum of healthy subjects with fatal injury) was subject to immune enzyme assay for determination of progesterone, estradiol, thyroxine, triiodothyronine, thyrotropic hormone, luteinizing hormone, follitropin, cortisol and prolactin [Chong A., Aw S., 1986]. The thyroid-stimulating hormone, luteinizing hormone, follitropin, cortisol and prolactin were revealed in the vitreous humour. As to other hormones, progesterone, estradiol, triiodothyronine and thyroxine, the results of immune enzyme assay were negative even despite their high solubility and relatively small size of their molecules. According to A. Steiger (2003), the role of somatotropin, somatostatin and adrenocorticotropic hormone (ACTH) in the genesis of a wide range of eye diseases with both inflammatory and degenerative genesis is also disputable.
The results obtained by mentioned authors testify in favour of the local synthesis of certain hormones in eye membranes and tissues.
It should be specially noted that regional neuroendocrine mechanisms underlying the induction of primary open-angle glaucoma have not been sufficiently studied yet. In this aspect the role of in situ produced cortisol in mechanisms of impaired ion exchange is exceptionally connected with disbalance of sodium ions transport between the cells and liquid media of an eye and the impaired catecholamines exchange.
As known, in peripheral “epithelial” tissues sodium and water transport are regulated by corticosteroids, 11-β-hydroxysteroid-dehydrogenase (11-β-HSD), its isoform (11-β-HSD1), due to which there occurs formation of cortisol molecule from cortisone. Considering this latter, some researchers [Rauz S. et al., 2003] determined levels of cortisol, cortisone, 11-β-HSD and 11-β-HSD1 in ciliary body of actually healthy volunteers. The study was aimed to reveal the role of cortisol and 11-β-HSD in regulation of intraocular pressure that is sustained due to balance of aqueous humour (intraocular liquid) depending on the sodium transport through the ciliated epithelium and drainage via the trabecular meshwork. In both study groups cortisol concentrations were higher than cortisone levels. In both groups oral application of carbenoxolone, 11-β-HSD inhibitor, was accompanied by a marked decrease of intraocular pressure. To our mind, data obtained by mentioned authors, on the one hand, signify in favour of the above-mentioned cascade of reactions for maintenance of intraocular pressure, on the other hand, in favour of cortisol local synthesis in post-barrier membranes of the eye.
There is an opinion, according to which merely 11-β-HSD1 ensures receptor Nf-dependent mechanisms through the ciliated epithelium, thus regulating the level of intraocular pressure [Rauz S. et al., 2001]. Mentioned authors revealed the fine mechanisms, which provide the level of glucocorticoids mediated intraocular pressure. However, the potentiating role of corticosteroids in regulation of intraocular pressure was revealed much earlier [Jacob E. et al., 1996]. As known, the rate of aqueous humour production is stimulated by adrenalin. The authors studied the joint and isolated effects of adrenalin and hydrocortisone to the rate of aqueous humor production in 20 volunteers. As demonstrated by study results, joint oral application of adrenaline and hydrocortisone significantly (by 42%) enhanced production of aqueous humour compared to placebo. The authors consider that both factors simultaneously function within the post-barrier membranes of the eye (ciliary body), thus ensuring the rate of aqueous humour production.
Molecular mechanisms underlying the biological action of glucocorticosteroids in eye membranes were also studied. Specifically, in the experiment, under conditions of cornea transplantation the influence of glucocorticosteroids (SEGRA) was studied to the labeled synthesis of anti- and pro-inflammatory cytokines. The application of glucocorticosteroids brought forth more efficient engraftment. Moreover, the terms of engraftment correlated with the low expression of cytokines, especially IL-I [Pleyer U. et al., 2005].
A. Southren et al. (1979) performed experiments in rabbits and revealed endoplasmatic reception of glucocorticoids in corneal cells and the ciliary body. Translocation of cortisol from the surface of the cell nucleus occurred within 30 minutes after injection. As to authors, this mechanism is a stereotype for glucocorticoids towards other sensitive tissues.
It is important to note the following phenomenon as well. Similar translocation was not observed when experimental animals were administered testosterone, estradiol and progesterone. At the same time, different membranes and liquid media of the eye possess different ability of affinity to glucocorticoids and their realization (accumulation and excretion).
In 1977, B. Kasavina et al. (1977) studied cortisol distribution in sclera, ciliary body, cornea, iris, lens capsule, vitreous body and the aqueous humour. Radionuclide methods of investigation allowed to reveal that tissues and media of the eye have different intensity of cortisol absorption and excretion. According to authors, the sclera, ciliary body, and lens capsule served as target tissues for cortisol.
3. Regional mediatory hormonal mechanisms of impaired eye drainage function at primary open-angle and pseudoexfoliative glaucomas (Results of own research investigation)
It is rather difficult to interpret issues relevant to pathogenesis of primary open-angle glaucoma, as this type malady is frequently associated with cataract and pseudoexfoliative syndrome.
In particular, according to D.S. Krol (1968; 1970), among the randomly selected contingent the pseudoexfoliative syndrome was observed in 6.2% subjects above 50, in 24% patients with senile cataract and in 47% patients with open-angle glaucoma. P.P. Frolova and G.Kh. Khamitova (1984) provided similar data, according to which pseudoexfoliative syndrome was diagnosed in 5.8% examined persons above 40. Furthermore, the higher the age, the more frequent was pseudoexfoliative syndrome encountered: at the age of 40-48 years old in 1% patients, at 50-59 – in 6.4%, at 60-69 – in 12.5%, above 70 – in 36.8%. It is especially important that among persons with pseudoexfoliative syndrome glaucoma was diagnosed in 35% cases, while cataracts made 69%.
According to clinical observations of A.P. Nesterov (2008) in persons with the pseudoexfoliative syndrome glaucoma originates 20 time more often than in the general population of the same age group. According to the author, approximately in 50% patients with open-angle glaucoma symptoms of pseudoexfoliative syndrome are revealed. The type of glaucoma associated with the pseudoexfoliative syndrome is called “pseudoexfoliative glaucoma”.
Nowadays, amongst the mechanisms of cataract induction and course, an importance is attributed to local immunepathological disorders, which all in all are defined as “anterior chamber associated immune deviation (ACAID) [Wilbanks G., Streilein J., 1990; Streilein J. et al., 1992; Abrahamian A. et al., 1995; Muhaya M. et al., 1999; Fleenor D. et al., 2006].
In pathogenesis of the primary open-angle glaucoma the specific gravity of regional immunepathological disorders, which are pathognomonic for cataracts, are open for a special discussion, because data of available scientific publications are scarce, fragmentary, sometimes contradictory and inconsistent.
At the same time, to our mind, it is rather expedient to perform studies at which in case of complicated cataracts associated with glaucoma and pseudoexfoliative syndrome the subject matter would be the entire specter of biologically active substances produced in eye membranes, which were earlier considered by us as pathogenetic factors of open-angle glaucoma. Such scientific and methodical approach is rather substantiated, as it will allow to answer the question: to what extent the processes of impaired synthesis of fibronectin, IGF-1, PgE2 and cortisol in eye membranes are engaged in mechanisms of primary open-angle glaucoma, namely: in pathogenesis of impaired drainage function and increase of intraocular pressure.
Under our observation there were 960 patients with the senile and complicated cataracts operated at “Shengavit” Medical Center within a period of 2008-2012. The degree of lens opacity was assessed according to Emery colorimetric classification and generally accepted classification of cataracts proposed by Buratto. Undoubtedly, the state of lens capsule, folding, presence of elements of fibrous filaments, pseudoexfoliative deposits on the anterior surface of the capsule, lens subluxation to some degree, were taken into consideration together with classification of phakodonesis suggested by Pashtaev. Actual expressiveness of the pseudoexfoliative syndrome was considered based on the classification proposed by Yeroshevskaya.
All operated patents were divided into three groups.
The studied groups of patients involved civil contingent: residents of Yerevan and different provinces (marzes) of Armenia; age range was from 40 to 82 years.
The first group included patients with senile cataract. The second group was made up of patients with the complicated cataract on the background of existing anterior open-angle glaucoma, with initial and developed stages of the glaucomatous process. The third group involved patients with complicated cataract on the background of existing pseudoexfoliative glaucoma and pseudoexfoliative syndrome.
The analyses were performed using the main clinical laboratory methods accepted in ophthalmology.
Irrespective of the cataract degree and stage, all patients underwent microaxial Phacoemulsification ‒ Microincision Cataract Surgery (MICS) through 2.2 mm incision with implantation of posterior chamber intraocular lens. Intra-chamber administration of antibiotics was not applied in these groups.
The methodical procedure of extracting aqueous humour was used intra-operatively under conditions of sterility. The corneocentis was done by insulin syringe through the limb; 0.1-0.2 ml aqueous humour was extracted. The fluid remained in a syringe until laboratory research was performed immediately after delivery of the material to the Scientific-Research Center of the Yerevan State Medical University after M. Heratsi.
All the operated patients were under intense observation and got the appropriate post-operative treatment and medical rehabilitation. We observed the patients in the early post-operative period.
Unfortunately, rather low amounts of isolated aqueous humour (0.1-0.2 ml) for immune enzyme assays and ion-selective analyses due to objective reasons, do not allow us simultaneously (in one and the same sample) determine two parameters of studied biological active compounds. Inclusion of a relatively high number of operated patients (by 320 persons) in each study group is connected with the mentioned circumstance. Thereby, in all the three study groups by 40 samples of aqueous humour and blood serum were allocated for each test.
The content of fibronectin, IGF-1, PgE2 and cortisol in aqueous humour was determined with the use of appropriate kits (DRG-International Inc., USA). The immune enzyme assay was performed on the automatic spectrophotometer “Stat-Fax 3200” (USA) in the absorbance wavelength range 420-450 nm.
Determination of potassium, sodium and calcium ions was done according to ion-selective method of analysis with use of Kone-microlyte analyzer (Finland).
The obtained results were exposed to statistical analysis using Student’s criteria and application of SPSS-13 programme (one Sample T-Test and Paired Sample T-Test).
The results of immune enzyme assay for fibronectin, IGF-1, and PgE2 in aqueous humour of patients with the senile and complicated cataracts are presented in Table 1.
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tStudy groups of patients\n\t\t\t
\n\t\t\t
\n\t\t\t\tStudied indices\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
\n\t\t\t\tFibronectin (ng/ml)\n\t\t\t
\n\t\t\t
\n\t\t\t\tIGF-1 (ng/ml)\n\t\t\t
\n\t\t\t
\n\t\t\t\tPgE2 (pg/ml)\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
I
\n\t\t\t
11.26±0.99
\n\t\t\t
1.10±0.18
\n\t\t\t
43.05±4.13
\n\t\t
\n\t\t
\n\t\t\t
II
\n\t\t\t
20.71±2.37 p1<0.0005
\n\t\t\t
2.50±0.46 0.0005<p1<0.005
\n\t\t\t
66.11±7.40 0.0005<p1<0.005
\n\t\t
\n\t\t
\n\t\t\t
III
\n\t\t\t
33.83±5.97 p1<0.0005 0.025<p2<0.05
\n\t\t\t
2.60±0.39 0.0005<p1<0.005 p2"/>0.4
\n\t
76.64±7.78 p1<0.0005 0.10<p2<0.25
\n
\n
Table 1.
Fibronectin, IGF-1, and PgE2 content in aqueous humour of patients with the senile and complicated cataracts
Notes: p1 –indices of groups II and III compared to indices of the study group I; p2 – indices of group II compared to indices of the study group III.
As obvious from the Table, in patients with cataracts on the background of primary open-0angle glaucoma (study group II) the level of fibronectin in aqueous humour 1.8 times exceeded analogous level in aqueous humour of patients with senile cataracts. In those cases when cataract was observed on the background of pseudoexfoliative glaucoma (study group III) the highest indices of fibronectin were determined in the aqueous humour; these indices were 3.0 and 1.6 times higher compared to those in patients of groups I and II, appropriately.
A similar regularity was traced upon revealing shifts in PgE2 and IGF-1 content in aqueous humour of patients in study groups I and II. Thus, the level of PgE2 in aqueous humour of the study group II patients 1.5 times exceeded PgE2 level in aqueous humour of the study group I patients. In study group III PgE2 high levels were also determined (compared to the study group I), being similar to those revealed in aqueous humour of the study group II patients. As obvious from the Table, in the aqueous humour of patients in study groups II and III we recorded approximately the same IGF-1 indices, which exceeded similar values in aqueous humour of study group I patients 2.27 and 2.36 times, correspondingly.
Table 2 presents the results of immune enzyme assay for determination of cortisol in the aqueous humour of patients with senile and complicated cataracts.
\n\t
\n\t
\n\t
\n\t
\n\t\t
\n\t\t\tStudy groups of patients\n\t\t
\n\t\t
\n\t\t\tStudied indices\n\t\t
\n\t
\n\t
\n\t\t
\n\t\t\tAqueous humour\n\t\t
\n\t\t
\n\t\t\tBlood serum\n\t\t
\n\t
\n\t
\n\t\t
I
\n\t\t
12.90±0.64
\n\t\t
56.90±4.15
\n\t
\n\t
\n\t\t
II
\n\t\t
23.38±1.46 р<0.0005
\n\t\t
64.84±7.28 0.1<р<0.25
\n\t
\n\t
\n\t\t
III
\n\t\t
30.4±1.56 р<0.0005
\n\t\t
50.70±6.91 0.1<р<0.25
\n\t
\n
Table 2.
Cortisol content in blood serum and aqueous humour of patients with the senile and complicated cataracts
Note: p – indices of complicated cataracts as related to indices of senile cataracts.
As obvious from Table 2, in patients of study group II the level of cortisol in aqueous humour markedly increased (as compared to hormone levels determined in aqueous humour of patients with the senile cataract – control group). Thus, the level of cortisol in aqueous humour of patients with cataract on the background of primary open-angle glaucoma was 1.8 times higher compared to norm. The highest indices of cortisol were observed in aqueous humour of patients of the study group III. In particular, cortisol levels in aqueous humour of patients with the senile cataract on the background of primary open-angle glaucoma and pseudoexfoliative glaucoma increased 2.3 times. The results of immune enzyme assays performed on aqueous humour were compared with cortisol levels in blood serum of the same cohort of patients. As demonstrated by the research findings, the level of cortisol in blood serum of patients of all the 3 study groups was almost similar and within the range of cortisol determined in actually healthy subjects. This latter, though indirectly, signifies in favour of the local synthesis of cortisol in the eye membranes, the cells of which apart from their main functions ensure processes of in situ cortisol secretion as well.
The next stage of our investigation involved biochemical analysis with the use of ion-selective method aimed to determine ions of sodium, potassium and calcium in the aqueous humour of patients with senile and complicated cataracts.
Table 3 presents results of analyses performed on the aqueous humour of patients with senile and complicated cataracts.
\n\t
\n\t
\n\t
\n\t
\n\t
\n\t\t
\n\t\t\tStudy groups of patients\n\t\t
\n\t\t
\n\t\t\tK+\n\t\t\t\n\t\t
\n\t\t
\n\t\t\tNa+\n\t\t\t\n\t\t
\n\t\t
\n\t\t\tCa++\n\t\t\t\n\t\t
\n\t
\n\t
\n\t\t
I
\n\t\t
5.00±0.21
\n\t\t
133.3±14.4
\n\t\t
0.99±0.06
\n\t
\n\t
\n\t\t
II
\n\t\t
2.30±0.26 р<0.0005
\n\t\t
177.6±17.2 0.025<р<0.05
\n\t\t
1.99±0.18 р<0.0005
\n\t
\n\t
\n\t\t
III
\n\t\t
1.92 ±0.28 р<0.0005
\n\t\t
196.7±18.2 0.005<р<0.01
\n\t\t
2.40±0.26 р<0.0005
\n\t
\n
Table 3.
K+, Na+ and Ca++ content in aqueous humour of patients with senile and complicated cataracts
Note: p – indices of complicated cataracts as related to indices of senile cataracts
As obvious from Table 3, the levels of K+, Na+ and Ca++ in aqueous humour of patients with senile cataracts were similar to those in actually healthy cohort of subjects (we compared indices of ions in aqueous humour of patients with senile cataracts with the indices indicated in monograph of A. Pirie and R. van Heyningen (1968)). In aqueous humour of patients with cataract on the background of primary open-angle glaucoma low level of potassium ions was determined, it was 2.2 times lower than the level in aqueous humour of patients from the study group I. The lowest indices of potassium ions were recorded in the study group III, i.e., at cataracts on the background of pseudoexfoliative glaucoma. Thus, the level of potassium ions in aqueous humour of this study group decreased 2.15 times.
Unlike the shifts in potassium content in the aqueous humour of patients from study groups II and III, regarding the increase of sodium and calcium ions content a diametrically opposite picture was observed in the same groups. The content of sodium ions in the study group II increased 1.3 times, in the study group III – 1.5 times, compared to corresponding indices in aqueous humour of patients with senile cataracts.
Similar tendency was also observed on calcium ions content in aqueous humour of patients from study groups II and III. Thus, the level of calcium ions in aqueous humour of patients with cataracts on the background of primary open-angle glaucoma was 2.0 times above the control (group I), while in patients with cataracts on the background of pseudoexfoliative glaucoma it was 2.4 times higher.
We considered purposeful to present interpretation of our research findings of immune enzyme assay for determination of fibronectin, IGF-1, PgE2, and cortisol in the aqueous humour of patients with cataracts associated with primary open-angle glaucoma and pseudoexfoliative glaucoma taking into account data of scientific publications relevant to sources for the synthesis of mentioned substances in specific eye membranes and their possible biological effects realized at the level of inter-cellular relations in different cell populations of the eye.
In line with this, first of all, we considered the essential role that is related to the biological activity of TGF2 produced in cornea and trabecular meshwork of an eye in mechanisms of inter-cellular relations in situ ensuring the drainage function of the eye.
It is considered to be generally accepted that in case of senile and complicated cataracts processes of TGFβ-2 synthesis are markedly intensified in the cornea and trabecular meshwork [de Iongh R.U. et al., 2005; Stefan C. et al., 2008; Dawes L.J. et al., 2009; Pattabiraman P.P., Rao P.V., 2010]. Therefore, we cannot exclude that relatively high levels of fibronectin and IGF-1 in the aqueous humour of patients with complicated cataracts are resulting from a direct stimulating influence of TGFβ-2 to cell populations localized in the cornea and trabecular meshwork of the eye selectively synthesizing fibronectin and IGF-1.
The proposed statement, to a known extent, is also confirmed by the available literature data relevant to the biological activity of TGFβ-2 – in the aspect of its selective modulatory impact to the processes of fibronectin and PgE2 synthesis and secretion in the eye membranes.
As known, keratocytes of the cornea and trabecular meshwork cells of the eye serve as the main sources of fibronectin synthesis in situ, i.e. in the eye tissues. Dose-dependent stimulant effect of TGFβ-2 to processes of fibronectin synthesis was established [Wordinger R. et al., 2007;\n\t\t\t\tHindman H. et al., 2010; Karamichos D. et al., 2010] under the conditions of mentioned cells cultivation. Moreover, according to [Stefan C. et al., 2008], TGFβ-2 produced in eye membranes should be considered as a “special” cytokine that under conditions of the eye barrier functions disturbance might increase fibronectin concentration in cells of trabecular meshwork of the eye anterior chamber’s angle.
The IGF-1 elevated level revealed in aqueous humour of patients with the complicated cataracts should be considered as a factor hindering drainage function of trabecular meshwork and thus facilitating the increase of intraocular pressure. It is not excluded that similar mechanism functions in association with fibronectin-dependent mechanisms underlying the disturbed drainage function of the trabecular meshwork in the senile and, moreover, in the complicated cataracts.
Literature data [Izumi K. et al., 2006; Yanai R. et al., 2006; Ko J. et al., 2009] signify in favour to the proposed assumption: IGF-1 produced in corneal epitheliocytes and cells of the trabecular meshwork significantly activates fibroplastic processes in situ. To our mind, in processes of IGF-1 enhanced synthesis in the above mentioned structures of an eye the role should be assigned to TGFβ-2 produced in the same eye membranes, because the latter is known to markedly activate synthesis of IGF-1 and mediators, which take an active part in stimulation of fibroplastic processes [Yamada N. et al., 2005; Izumi K. et al., 2006; Ko J. et al., 2009], in corneal epitheliocytes and cells of trabecular meshwork.
In the light of our own and literature data, the role of TGFβ-2 in mechanisms of ACAID induction and withdrawal should be considered from qualitatively new positions. No doubt, the immunomodulatory effect of TGFβ-2\n\t\t\t\tin situ that is conditioned by the targeted activation of the cytotoxic lymphocytes subpopulations (T-suppressors and T-killers) is determinant in processes of forming intercellular correlation among different lymphocytic subpopulations localized in eye membranes, hence ensuring reactions underlying ACAID. However, it is not excluded that the sphere of TGFβ-2 activity under conditions of norm is more versatile, as in situ produced mentioned cytokine directly and/or indirectly (activating the synthesis of fibronectin and IGF-1 in a mediated manner) participates in processes of maintaining the drainage function of trabecular meshwork, thus ensuring the constant level of intraocular pressure. Apparently, the above-mentioned mediatory effects of TGFβ-2 are strictly dose-dependent, as under conditions of pathology (in the given case: at senile and, especially, at the complicated cataracts) a significant elevation of TGFβ-2 in eye membranes brings to trabecular meshwork dysfunction; the latter is fraught with the increase of intraocular pressure.
The analysis of our own research results in the context of available publications allows to consider the important role of TGFβ-2 and IGF-1, which are produced in cornea and trabecular meshwork, in mechanisms ensuring the drainage function of an eye.
The facts of detection of receptors to PgE2in cells of trabecular meshwork and sclera allow possibility of PgE2 participation in processes of intraocular pressure regulation.
The high level of PgE2 found by us in aqueous humour allows possibility of its participation in processes of the impaired drainage function and increase of intraocular pressure at cataracts proceeding on the background of primary open-angle glaucoma pseudoexfoliative glaucoma.
The following phenomenon of no less importance should specially mentioned: high levels of fibronectin IGF-1 and PgE2 in the aqueous humour of patients under study were pathognomonic for the course of the primary open-angle glaucoma and not for cataracts, as in this latter case all the indices studied in aqueous humour were much lower than analogous indices at senile non-complicated cataract.
Our research revealed a direct correlation dependence between the high level of cortisol, on the one hand, and the content of sodium and calcium ions, on the other hand. Based on the results obtained a conclusion might be drawn that the increase of intraocular pressure in persons with complicated cataracts on the background of glaucoma is mostly conditioned by impairment of ion transfusion between the ciliary body and aqueous humour and the processes of cortisol “hyperproduction” by hormone-producing cells in post-barrier membranes of the eye.
4. Conclusion
This chapter deals with one of the urgent problems of modern ophthalmology: revealing the mechanisms underlying induction of primary open-angle and pseudoexfoliative glaucoma. Till nowadays the problem remains rather actual, as the issue is open to discussion: what are the regional mechanisms underlying the disorders in functions of the trabecular apparatus of the angle of anterior chamber of an eye and in the increase of intraocular pressure at the mentioned disease case.
One of severe complications of glaucoma is the steady persistent increase of intraocular pressure that is fraught with compression of the head of optic nerve that results in its partial or complete atrophy with the partial and/or complete sight loss. Currently, the majority of specialists engaged in clinical and experimental ophthalmology are inclined to the opinion that the increase of intraocular pressure is not the consequence of general hemodynamic disorders resulting from the permeability increase in hematoophthalmic barrier, but rather originates from pathological processes occurring in the membranes and chambers of an eye.
In line with the modern views, processes underlying the increased intraocular pressure originate in the eye structures as such: in connective-tissue, epithelial and endothelial cells of the ciliary body, cornea, retina, lens, trabecular apparatus of the angle of the anterior chamber of an eye. These cells possess selective secretory activity in the aspect of producing a number of biologically active substances exerting direct and/or indirect action to the processes regulating intraocular pressure.
Moreover, numerous pathological processes proceeding in case of primary open-angle glaucoma at the site of eye membranes are fraught with the infringement of chamber humour osmolarity; furthermore, one of mechanisms increasing the volume of aqueous humour and not infrequently hindering its outflow is the impaired K+/Na+ balance in favour of the accumulation of this latter in the anterior chamber of an eye.
Available literary data of the last 30 years which discuss mediatory functions realized by cells of fibroblastic, epithelial and endothelial line in a ciliary body, cornea, retina, lens, a trabecular network formed a basis for carrying out the research directed at clarification of a role of in situ produced fibronectin, IgF-1 and a cortisol at primary open-angle glaucoma.
The drainage function of trabecular meshwork of an angle of the anterior chamber of an eye is an active process, in which the leading role belongs to secretory cells of this network. As it was specified above, secretory cells of the trabecular meshwork develop TGFβ-2, fibronectin and an insulin-like growth factor -1, PgЕ2. It is not excluded that the mentioned substances play an important role in ensuring drainage function of a trabecular meshwork, and thus, to a certain extent, in maintenance of an optimum level of the intraocular pressure.
For this reason, high indices of fibronectin and IGF-1 found in aqueous humour of patients with primary open-angle glaucoma testify in favor of hypersecretion of mentioned cytokines by cells of a trabecular meshwork. The presence of fibronectin and insulin-like growth factor-1 high concentrations at the primary open-angle glaucoma, and also at pseudoexfoliative glaucoma, testifies to violation of drainage function of a trabecular meshwork of an angle of the anterior chamber of an eye; this latter, to a certain extent, preconditions the high level of intraocular pressure. At the same time, the specific weight of fibronectin and insulin-like of growth factor -1 in hypertension formation in the aqueous humour is far from being equivalent, as on the one hand, fibronectin level in aqueous humour of patients from investigated groups II and III 10 times exceeds concentration of insulin-like growth factor-1 in the same liquid, on the other hand, as known, the weight of soluble fibronectin makes 440.000-150.000 D, while the mass of insulin-like growth factor-1 is 7.649 D [Panteleev M. A. et al., 2011].
Thus, on the basis of the analysis of literary data and carried-out own research it is possible to conclude that at glaucomas the infringement of drainage function and increase of intraocular pressure is in many respects caused by high concentration of fibronectin and, partially, insulin-like growth factor-1 in the intraocular liquid.
As it was noted above, the content of PgЕ2 considerably increases in aqueous humour of patients with primary open-angle glaucomas and pseudoexfoliative glaucomas.
There is scanty literature about the synthesis of prostaglandins in eye membranes. Local synthesis of prostaglandins is found out only in cells of crystalline lens that was proved by research of O. Nishi et al. (1992) in model experiments in vitro: at cataract the extracted lens in the course of operation was located on incubation medium. With the increase of incubation terms the content of prostaglandins Е2 in the incubation environment considerably increased. At the same time, in a number of eye membranes, the ciliary body, sclera and the trabecular meshwork of an angle of the anterior chamber of an eye receptors to prostaglandins Е2 were found [Toris C.B. et al., 2008].
It is not excluded that the high content of PgЕ2 in aqueous humour is fraught with an increase of intraocular pressure at glaucomatous patients, as according to [Podos S.M. et al., 1972 a; b; Podos S.M., 1976 a; b; c], PgЕ2 takes an active part in maintenance of drainage function of an eye.
It is known that ionic balance in liquid media of an organism (blood, spinal, gingival, synovial and intraocular liquids) is a necessary condition for maintenance of the osmotic pressure.
The anterior and posterior chambers of an eye are main depots; water makes about 93% and a very insignificant share make proteins. It is considered established that the delay of outflow of aqueous humour or its intensive more “production” promotes considerable elevation of pressure inside an eye.
Thus, one of the factors leading to increase of intraocular pressure at glaucomas is the increase of osmolarity of intraocular liquid.
It is considered to be established long ago that at anterior open-angle glaucoma in aqueous humour there are serious impairments in its ionic structure that was shown by disorders in functioning of sodium ‒ potassium pomp, with the superfluous accumulation of sodium ions.
In our research as demonstrated by the results of ion-selective analysis, at primary open-angle glaucomas and pseudoexfoliative glaucomas rather high indices of ions of sodium and calcium and low indices of potassium were determined in aqueous humour, as compared with the indices defined in aqueous humour of patients with senile not complicated cataracts.
The similar imbalance, being shown as superfluous accumulation of sodium and calcium in aqueous humour, complicates normal outflow of aqueous humour from the anterior chamber of an eye that, in its turn, is fraught with the increase of intraocular pressure.
Without considering the questions connected with mechanisms of shifts found by us regarding electrolytes content in aqueous humour (that was not an actual problem of the present research), nevertheless we consider expedient to discuss some aspects connected with the fact established by us on impaired ionic balance between eye membranes and the intraocular liquid.
Firstly, the increase of Na+ and Ca++ levels observed by us in aqueous humour should be considered from positions of the broken ionic balance between specific membranes of an eye and intraocular liquid, and not as a result of the general disorder of electrolytes composition in blood of experimental animals, because the level of studied electrolytes in blood serum was within the limits of control values.
Secondly, the high level of a cortisol found by us in aqueous humour can serve one of possible causes of infringement of the ionic balance. This assumption appears very reasonable, as it is known that high concentrations of cortisol in separate membranes of an eye lead to ionic imbalance in connection with enhanced inflow of ions of sodium in aqueous humour that results in an increase of intraocular pressure.
Thirdly, it is not excluded that realization of hormonal and cytokine-dependent processes conditioned by regional shifts in the content of cortisol, prolactin, fibronectin, insulin-like growth factor-1 at cataracts proceeding on the background of primary open-angle glaucoma and pseudoexfoliative glaucoma, is caused by activation of calcium-dependent reactions in secretory cells of eye membranes.
It is considered established that the pseudoexfoliative syndrome represents itself as a provoking factor for development of the open-angle glaucoma, the course of which has a progressing character and is characterized by high resistance to carried-out medicamentous therapy and an unfavourable forecast [Prince A.J, Ritch R., 1986; Streeten B.W. et al., 1990; Tarkkanen A. et al., 2002; Takhchidi K.P. et al., 2010].
One of severe complications at development of a pseudoexfoliative syndrome is cataract as well [Küchle M. et al., 1997; Puska P., Tarkkanen A., 2001].
The impairment of immunological tolerance (of immunological privileges of an eye – ACAID) acts as an initiating factor for development of pseudoexfoliative syndrome [Takhchidi K.P. et. al., 2010].
It is not excluded that in pathogenesis of pseudoexfoliative syndrome emergence are also involved the local hormonal-mediatory mechanisms connected not with the operational intervention, but rather with infringement of processes of synthesis and secretion of such cytokines as TgFβ-2, IGF-1 and, first of all, fibronectin in cornea, ciliary body and trabecular meshwork of synthesis.
At a pseudoexfoliative syndrome essential physical and chemical changes occur in aqueous humour: the concentration of proteins considerably raises, including fibronectin as well [Takhchidi K.P. et al., 2010]. At the same time, shifts found by us in aqueous humour of patients with cataract on the background of pseudoexfoliative glaucoma, in many respects depend on the character of disease course: not so much of cataract, as glaucoma and the pseudoexfoliative syndrome. It is not excluded that in this studied group the high level of fibronectin in aqueous humour in many respects depends on features of pseudoexfoliative syndrome development.
On the basis of the analysis of literary data, it is possible to come to conclusion, according to which TGFβ-2 developed in eye membranes plays far not the last role in pathogenesis of primary open-angle glaucoma, including pseudoexfoliative glaucoma as well. So, at glaucomas of TGFβ-2 stimulates synthesis of such cytokines as insulin-like growth factor-1 and fibronectin in cornea, ciliary body and a trabecular meshwork of an angle of the anterior chamber of an eye. Their high levels found by us in aqueous humour testify to possible violation of drainage function of the trabecular meshwork that is fraught with an increase of intraocular pressure.
In conclusion, in the form of generalized schemes 1 and 2 the possible pathogenetic links engaged in the induction and a course of primary open-angle glaucoma, including pseudoexfoliative glaucoma as well, are presented to attention of ophthalmologists. The specific subject matter is regional disorder that is fraught with impairment of secretory activity of the polypotent cells localized in various eye membranes, which besides the main functions produce a number of biologically active substances of the cytokine, hormonal and mediatory nature.
At anterior open-angle glaucoma (see schemes 1 and 2) the synthesis of fibronectin in cells of the trabecular meshwork is considerably activated which is caused by the stimulating influence of fibroblasts transforming growth factor (TGFβ-2). Realization of this effect, to a certain extent, is caused by blocking of inhibitory effect of a bone morfogenic protein (BMP-4) towards the activity of TGFβ-2 due to which the stimulating effect of the latter on processes of fibronectin intra-cellular synthesis is realized. It is not excluded that at the same time there occurs blocking of inhibitory effect of TGFβ-1 on domain of heparin (Hep-2) responsible for synthesis of fibronectin in a cell.
Further, as a result of fibronectin “hyper production”, there is a deposition of fibronectin in extracellular matrix (EM) owing to which, as a result of drainage function impairment in trabecular meshwork, there proceeds an increase of intraocular pressure.
It is not excluded that in the conditions of physiological activity of trabecular meshwork cells the processes of intra-cellular synthesis of fibronectin are regulated according to cytokine mechanisms in realization of which, on the one hand, TGFβ-2 serves as a stimulating factor, on the other hand, this stimulating effect is adjusted due to gremin (G) and BMP-4 produced in trabecular meshwork cells. It is precisely the coordinated activity of aforementioned cytokines, TGFβ-2, G and BMP-4, that strictly supervises the balanced synthesis of fibronectin cells by trabecular network cells in the conditions of norm.
The specified Scheme 1 was constructed by us upon the analysis of the modern data concerning a role fibronectin, which is produced in keratocytes and cells of a trabecular meshwork, in violation of the drainage function of an eye at glaucomas and complicated cataracts [Gonzales J.M. et al., 1998; Fleenor D. et al., 2006; Wordinger R.J. et al., 2007; Stefan C. et al., 2008; Zilfyan A., 2009; 2012; Hindman H.B. et al., 2010].
In addition, due to analysis of the modern scientific data in the aspect of our own research findings we propose a summary scheme (Scheme 2) that presents the role of in situ produced biologically active compounds, which under conditions of disorders in synchronous activity of secretory cells localized in various membranes of the eye might bring to impairment of the drainage function and development of a symptom complex that is characteristic for primary open-angle and pseudoexfoliative glaucoma.
Scheme 1.
The role of trabecular meshwork cells of the anterior chamber angle of an eye in mechanisms of fibronectin-dependent drainage function impairment and the increase of intraocular pressure at anterior open-angle glaucoma
Scheme 2.
The role of mediators and hormones in mechanisms of intraocular pressure increase at complicated cataracts: cataracts on the background of primary open-angle glaucoma and pseudoexfoliative glaucoma
As obvious from Scheme 2, regional factors engaged in mechanisms of drainage function impairment and intraocular pressure increase might be conditionally divided into 2 categories. Secretory processes associated with dysfunction of cornea and trabecular meshwork cells (in the aspect of their targeted synthesis of TGFβ-2 should be related to category 1. Category 2 should embrace hormonal disorders, impairment of the regional ionic homeostasis and destructive processes, mechanisms of which are not sufficiently studied until present. In the given scheme we consider only 1 point of application that is affected by the influence of all the above mentioned factors: as a “target” here serves the trabecular meshwork of the anterior chamber of an eye with impaired drainage function that eventually rings to an increase of intraocular pressure. As evident from Scheme 2, in case of anterior open-angle glaucoma the regional TGFβ-2 dependent mechanisms are engaged, being conditioned by its stimulating influence to secretory cells of some eye membranes: in the aspect of their “excessive” synthesis of fibronectin and IGFβ-2, which cumulate both in stroma of the trabecular meshwork and in the aqueous humour finally resulting in block of drainage system and an increase of intraocular pressure. The hyperproduction of PgE2 in secretory cells of trabecular meshwork, sclera and, probably, the lens, also brings forth impairment of the drainage function. In impairment of drainage network functions a definite role is also devoted to in situ produced cortisol and processes resulting in disorders of ionic balance between the membranes and liquid media of an eye (first of all: between the cells of the ciliary body, cornea, trabecular meshwork and the aqueous humour). In the mechanism of impaired ionic balance that at the primary open-angle glaucoma is characterized by excessive accumulation of sodium ions in aqueous humour a certain part belongs also to cortisol produced in eye membranes. In cases of pseudoexfoliative glaucoma deposition of pseudoexfoliative matter in the anterior segment of an eye might cause blocking of the drainage system.
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Zilfyan",authors:[{id:"157235",title:"Dr.",name:"Artashes",middleName:"Arto",surname:"Zilfyan",fullName:"Artashes Zilfyan",slug:"artashes-zilfyan",email:"zilf.art@mail.ru",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/157235/images/3864_n.jpg",institution:{name:"Yerevan State Medical University",institutionURL:null,country:{name:"Armenia"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Secretory-mediatory hormone-dependent functions of eye membranes in the mechanisms of glaucoma development",level:"1"},{id:"sec_2_2",title:"2.1. The role of transforming growth factor β-2 (TgFβ-2), insulin-like growth factor-1 (IgF-1) and Е2 prostaglandins (PgE2) in pathogenesis of primary open-angle glaucoma",level:"2"},{id:"sec_3_2",title:"2.2. The role of fibronectin in pathogenesis of primary open-angle glaucoma",level:"2"},{id:"sec_4_2",title:"2.3. The role of cortisol in pathogenesis of anterior open-angle glaucoma ",level:"2"},{id:"sec_6",title:"3. Regional mediatory hormonal mechanisms of impaired eye drainage function at primary open-angle and pseudoexfoliative glaucomas (Results of own research investigation)",level:"1"},{id:"sec_7",title:"4. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'AbrahamianAXiMDonnellyJRockeyJEffect of interferon-gamma on the expression of transforming growth factor-beta by human corneal fibroblasts: role in corneal immunoseclusion. J. Interferon Cytokine Res. 1995154323330'},{id:"B2",body:'BanhADeschampsP. AGauldieJOverbeekP. ASivakJ. GWest-maysJ. ALens-specific expression of TGF-beta induces anterior subcapsular cataract formation in the absence of Smad3. Invest. Ophthalmol. Vis. Sci. 2006Aug; 47834503460\n\t\t\t'},{id:"B3",body:'BucciF. AJr., Waterbury L.D. Comparison of ketorolac 0.4% and bromfenac 0.09% at trough dosing: aqueous drug absorption and prostaglandin E2 levels. J. 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Zilfyan",address:"namj@ysmu.am, zilf.art@mail.ru",affiliation:'
Scientific-Research Center, Yerevan State Medical University, Yerevan, Armenia
“Shengavit” Medical Center, Yerevan, Armenia
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1. Introduction
Coffee is an everyday beverage and consumed enthusiastically throughout the world. This popular beverage is a primary source of annual income and employment, contributing economically, on four continents, as well as too many emerging nations. In the second half of the nineteenth-century coffee was transformed into an industrial product as a consequence of the accelerated expansion of coffee production in Brazil, which in turns, nurtured the growth of a mass consumer market in the United States [1].
Coffee crop, in current times, spread in over 10 million hectares grown in more than 80 tropical and sub-tropical nations. On a social basis, it plays a relevant role notably for the subsistence of nearly 20 million coffee-farming families in underdeveloped countries of Asia, Africa and Latin America [2]. In the world, coffee places in the second-largest export commodity position only behind to the petroleum products [3].
According to the USDA 2020/21 Forecast Overview [4], the world coffee production is estimated at approximately 9 million bags (60 kilograms) superior to the past year record of 176.1 million. The forecast is that Brazil accounts for most considerable of the increment because its arabica coffee crops start the on-year of the biennial production cycle and robusta coffee is achieving record output. Brazil is the leading supporter of the forecast for the expansion in world exports. Arabica output in Brazil is forecast to achieve 6.8 million bags above the preceding season to 47.8 million. Most favorable climate conditions prevailed in the majority coffee regions, promoting coffee fruit setting and development and filling, thus succeeding in high yields.
The genus Coffea includes approximately 124 well-identified species. Coffea canephora P. and Coffea arabica L. are commercially highpoints species [5]. C. arabica is a member of the family Rubiaceae and is a single polyploid species inside the genus Coffea. This true allotetraploid has 2n = 4x = 44 chromosomes. It is the old and most cultivated species of a coffee plant [6, 7]. Concerning floral biology, each species of the Coffea genus has its particularities and C. arabica can be characterized as self-fertile, it means that reproduction occur through self-fertilization, with an allogamy index of about 10%, on average. One research carried out at the Instituto Agronômico de Campinas concluded that insects (bees in particular), wind and gravity, are the main responsible for the pollination of coffee [8].
Genetic diversity is a prerequisite component of biodiversity, obligatory for species reproduction, and essential for adapting species to a dynamic environment [9]. Besides, assessment of genetic diversity directly impacts the development of new varieties through breeding. So, valuable genetic traits can be transferred to existing plant cultivars to achieve goals towards increasing crop yields, characteristics related to the quality of crops, resistance to disease and pest, etc. Plant breeding focused on wild races genetic information is usual for most global crops and has driven an essential contribution to increasing global food security [10]. Notwithstanding, genetic information wild races have been reduced at an alarming rate, specifically for tropical crop species, including C. arabica [11, 12]. Among other expert scholars, Labouisse et al. [13] cite deforestation as a noticeable contributing factor affecting the genetic erosion of coffee in Ethiopia. McNeely et al. [14] states some issues like land use conversion, overexploitation, and introduction of exotics species as factors contributing to native populations decimate.
In plant breeding, it is decisive to identify the most critical phenotypic traits to increase plant production. Therefore, the assessment of trait occurrences and dissimilarities in a population is the key to defining possibly useful crosses among accessions. The first line of attack is to understand the extent of the variability of some species. To do that, many countries around the world strategically centered money and human capital on collecting, assessing, and keeping the genetic resources available on germplasm banks. Although many studies emphasize the genetic diversity with molecular markers, it is also useful for plant breeders to contemplate the morphological and agronomical diversity of interest traits. In this context, we briefly show the coffee chain’s budget value, summarily point out the leading germplasm banks, and concisely demonstrate the employment of genetic diversity assessed on morphological and agronomical traits, along with molecular markers approaches.
2. Economic importance of Coffea arabica
Coffee represents an agricultural commodity that has stood out in international trade and domestic supply in terms of quantity and value [15]. Developing countries correspond to the leading suppliers, while the main buyers are developed countries, in which coffee consumption is full-bodied. The soil characteristics of the intertropical and equatorial regions of the world play a fundamental role in the coffee marketing chain worldwide [16].
Approximately 170 countries are coffee producers, and almost all countries are consumers, highlighting its commercial importance, which has grown steadily over the last 150 years [17]. Even with the crop distribution range, it has not represented a barrier to the growing production concentration in some nations. Currently, 70% of the consumed coffee worldwide comes from Brazil, Vietnam, Colombia, and Indonesia. In contrast, the primary consumer countries are the United States, the European Union, Brazil, and Japan, which account for two-thirds of the global demand for coffee [16].
Agricultural products usually have limited extended storage to avoid severe losses of quality. However, in coffee, the beans can be stored for decades, since observed aspects regarding the limits of humidity, light, temperature, and the latter keeping with reasonable consumption conditions. The coffee profile allows coffee growers to use the harvest with a strategic vision of economics. Many of them prefer store in bags instead of selling them immediately, hoping they will reach better prices [16].
Coffee was introduced in Brazil in 1727 through French Guiana and spread from northern Brazil to the southeast states, mainly in the mountain regions. Coffee developed in these areas due to favorable climate conditions for its grown, such as mild temperature, heavy rains, and distinct dry season [18].
The cultivation of coffee has evolved significantly and contributed to economic development throughout the history of Brazilian regions, particularly during early times and locations where the crop implantation occurred. The establishment of farming dates back to the 18th century in the northern land, precisely at the State of Pará. Later, it moved to the states of Rio de Janeiro and São Paulo (which corresponds to the Paraíba Valley). In 1850, cultivation spread rapidly towards Serra da Mantiqueira and Santos. In the 20th century, coffee cultivation continued its expansion in the states of São Paulo, south of Minas Gerais, Espírito Santo, Paraná and also to the northern region of Brazil, in the State of Rondônia. During this period of growth, the Brazilian economy, in general, was strongly associated with the coffee market, and the Brazilian Federal Government heavily regulated the coffee market until the mid-1990s [19].
Twelve states represent the primary coffee-producing regions in Brazil, and there are about 300,000 coffee plantations in the country, spread over 1950 cities is estimated. The state of Minas Gerais holds about 50% of the total coffee production in Brazil. Minas Gerais state offers topography and mountain climate ideal for the cultivation of coffee that along with the low-cost land, and abundance of cheap labor, may contribute to their outstanding position [20].
Minas Gerais accounts for approximately 50% of coffee cultivated in Brazil, 98% of this occupancy with C. arabica species that is the most economically relevant species. Some of the most economically outstanding cultivars of C. arabica in Brazil are Mundo Novo, Bourbon, Catuai Vermelho, and Catuai Amarelo [21].
At world scenario, the International Coffee Organization estimated that in 2014, the consumption of coffee was 150.3 million bags of 60 kg, in 2015; it rose to 152.1 million bags. In the last four years, the annual increase has remained an average of 2%. There was a significant increase in consumption in the Asia region, with rates of growth in the range between 4.5 and 9% in Indonesia, the Philippines, India, and Thailand. World coffee production in 2015 was 143.4 million 60 kg bags [22].
In April 2020, analyzing world coffee exports, it appoints an estimate to the 10.82 million bags, whereas, in April 2019, this number was 11.17 million. In the first seven months of the coffee year from 2019 to 2020 (the period between October/19 to April/20), they decreased 3.8% concerning exports in the same period from 2018 to 2019, totaling 72.78 bags, against 75.67 million. Shipping of beans of C. arabica species in the 12 months ending in April 2020 totaled 81.30 million bags, against 80.75 million bags the previous year [23]. In this context, Brazil has been responsible for 20% of coffee exports in the world. Due to the exponential growth of global consumption and the capacity to produce in large quantities, Brazil has become one of the largest coffee beans exporters. In numbers, it represents more than 34 thousand bags, which corresponds to the US $ 5.4 billion in revenue, 15% of which consists of Specialty coffee. The United States and Germany are the major importing countries [24]. The coffee tree farmland employs approximately 26 million people, many of whom are small farmers, dependent mainly on coffee for their livelihood [25].
In the budgetary part, the International Coffee Organization’s composite indicator fell 4.1% in May 2020, registering an average of 104.45 US cents per pound, which represented a second consecutive month of decline. The price trend curve for all C. arabica groups was bearish. From October 2019 to April 2020, shipments from Africa increased 7% to 7.66 million bags, and those from Asia and Oceania increased by 0.6%, to 23.62 million bags. In the same period, shipments from Central America and Mexico fell 4.9% to 8.77 million bags, and those from South America fell 8.6% to 32.74 million [23].
A series of research recognizes the economic value of genetic diversity [26]. However, these authors confirm the market failure in the case of conservation of coffee genetic resources, especially in Ethiopian highland forests, alerting that in 10 years, the coffee forest will disappear if the current devastation rates persists, which is alarming. This study addressed Ethiopian genetic coffee resources, the primary centre of diversity, revealing the potential economic importance of amounts to nearly US$1458 million, considering a 5% discount rate and US$420 million for a 10% discount rate. A good explanation of this outsized discount rate impact may be the expressive time lag between the required cost of coffee breeding programmes and the gains resulting from enhanced cultivars development.
3. Origin and distribution of Coffea arabica
The study of plant domestication, beyond its role in man’s cultural evolution, is an excellent experimental system for the study of biological evolution. Numerous dissimilarities in the middle of wild and domesticated types are related to essential features and basic plant biology processes, such as adaptation, development, and reproduction [27].
The C. arabica had its origin in the highlands of tropical forests located in southwestern Ethiopia. Under the specter of the biological structure, the genetic basis of the world’s coffee plantations is considerably small, as are most commercial coffee varieties to date, derived from a limited number of accessions from Ethiopia’s forests [26].
C. arabica is one of the most favorite beverage crops globally that accounts for about 70% of the total international coffee market. This crop species is the most valuable globally due to their high beverage quality and taken every day by a million people worldwide. The C. arabica was assumed to be originated in the Southwestern part of Ethiopia in specifically called the Keffa area [28]. It is also considered the possibility that C. arabica was originated in the Boma plateau in Sudan and Mount Marsabit of Kenya. Ethiopia is recognized strongly substantiated as a primary centre of diversity for coffee arabica [29, 30, 31].
In ancient times, coffee was first noticed by the Arab merchants in Ethiopia and taken to Yemen [32]. The origin of C. arabica has been subject to both molecular and archeological studies, confirming the Ethiopian origin of C. arabica [28, 33, 34]. C. arabica is a true allotetraploid species with 2n = 4x = 44 that considered as originated from the interspecific hybridization of C. canephora and C. eugenioides [35, 36].
C. arabica cultivation was started after the wild coffee introduced from Ethiopia to Yemen as early as 575 AD [32]. The cultivated coffee arabica divided in to C. arabica var. typica and C. arabica var. Bourbon [37]. After its introduction to Yemen, the coffee arabica was distributed worldwide and became the most popular beverage crop. The crop distributed to Reunions Island from Yemen and then introduced to India and Java (Indonesia) [38, 39]. The coffee crop was then distributed from Java to Europe (Amsterdam botanical garden) in 1710 [28, 40]. After that, the coffee plant was taken to South America in 1718 from Europe. It was introduced to Martinique Island in 1720 or 1723 and Brazil via French Guiana in 1727 [40, 41, 42]. Finally, the coffee was spread throughout the world from South America. Ferreira et al. 2019 [43] precisely illustrate the origin and dispersion of C. arabica (Figure 1).
Figure 1.
Origin and dispersion course of Coffea arabica all the way through the world. Image reproduced from reference [43] with permission from the Royal Society of Chemistry (RSC).
4. Coffea arabica genetic resources
The efficient use of available germplasm for breeding purposes requires detailed information on the relationship of genetic relatedness among accessions that compose it, primarily affected by the domestication process. The prospect of coffee improvement in all desirable aspects depends on the availability and use of the mostly untapped genes found in the wild, in farmers’ fields and in and ex-situ germplasm collections [3].
Conservation in-situ of plant species make possible the maintenance a greater diversity of species and genepools in a dynamic environment, supporting populations that continue to evolve [44]. Understory trees in the tropical forests of Africa are the range where wild coffee grows spontaneously. It covers a wide geographic area from Guinea in West Africa through Central to eastern Africa, with additional centres of diversity add the Mascarene Islands (La Réunion and Mauritius) in the Indian Ocean, Madagascar, and the Comoros Islands [45].
From 1971 and 1997, the deforestation took place in around 235,400 ha of closed and slightly disturbed forests in the highland plateau of southwest Ethiopia. Numerous international organizations have outlined proposals for in-situ conservation of C. arabica, but regrettably, implementation has been lagging as a result of financial constraints [46].
An effort to preserve the last remaining coffee forests in Ethiopia and to prevent the loss of biodiversity resulted in a creation of the Yayu Biosphere Reserve and the Kafa Biosphere Reserve, in 2010. At that time, due to the sustainable strategic interest, it became component of the United Nations World Network of Biosphere reserves. Yayu Coffee Forest Biosphere plays a crucial role in the in-situ conservation being the last remaining montane rainforest fragments with wild C. arabica populations in the world [47].
Given this alarming scenario, in the past, the strategic importance of wild C. arabica boosted exploration missions guided to in its primary centre of origin (Ethiopia and Kenya) and the secondary centre of diversity, Yemen. In this sense, in 1964–1965, a Food and Agriculture Organization of the United Nations (FAO) conducted collecting expedition of coffee germplasm in different locations in Ethiopia [48]. In 1966, an expedition mission performed by ORSTOM (Office de la Recherche Scientifique et Technique Outre-Mer; a formerly designation of Institute de Recherche pour le Développement [IRD]) collected germplasm from 70 different origins. Despite the original purpose, most accessions were collected from cultivated coffee being only some native of the understory of tropical forest [49].
The accelerated devastation of the tropical forest ecosystems in Africa, Madagascar, the Comoros and Mascarene islands drove collecting mission for other Coffea species. The result of those collecting expedition yielded a total of 20,000 wild coffee trees collected, representing more than 70 species and also the identification of 300 wild coffee populations [49].
According to Bramel et al. [31], is consensus in the majority of institutions worldwide indicates the conservation of the collection is secure due to the adherence and engagement of the institutes and their team. In most institutions, everyone is challenged, to some degree, to cover the yearly cost for everyday conservation operations. One critical study concerning costing for Centro Agronómico Tropical de Investigación y Enseñanza (CATIE) confirms the long-term implications of negligence if the fund is insufficient, which is quite alarming.
Comprehensively, the conservation tactics applied to C. arabica accessions may be in-situ sites or both ex-situ and in-situ. In-situ involves the maintenance of genetic material in the arrangement of native populations by implementing ecosystem reserves such as national parks and refuges. On the order hand, ex-situ that deals maintenance of a species out its original habitat. In this approach, farmed and natural plant species are collected and transferred to a specific site aiming to conserve the genetic information. Furthermore, the accessions are maintained locally in the forms seeding, seeds or in vitro culture [31].
In this sense, the chief way of knowing and measuring the size of species variability is to carry out collection expeditions to acquire materials in a vast natural geographic occurrence. After that, each accession must be documented, and subsequently, the measurement of its phenotype must be carried out. In germplasm conservation ex-situ, the most common scheme used in coffee, this surveying must be made with suitable statistical designs, plot sizes suitably reliable, an adequate number of repetitions and field locations.
According to Giomo et al. [50], the first and critical step in a breeding programme is the presence and understanding of genetic diversity. In this sense, the knowledge of a series of desirable traits is required to develop a new cultivar of coffee such as adaptability, architecture, fruit color, longevity, maturation, precocity, productivity, resistance to pests and diseases, size, type of grain, quality of coffee cupping, vigor, among others. Therefore, it is imperative to know the distinguished accessions selecting particular interest traits, including agronomic characterization of plants up to the beans’ chemical composition and sensory quality, to meet the specific coffee production chain demands.
In coffee species, a significant marketable crop, the research on genetic improvement carried out by a renowned research center around the world has in the germplasm banks its primary source of raw material, essentially in C. arabica and C. canephora. Germplasm banks guard and preserve an extensive collection of genetic resources used in breeding research and biotechnology to obtain increasingly adapted and productive cultivars.
Among the world-leading significant germplasm resources and conservation of the Coffea genus, we highlight the following research institute: Centre National de Recherche Agronomique (CNRA), United States Department of Agriculture - National Plant Germplasm System, CATIE, Centro de Cooperación Internacional de Investigación Agricola para el Desarrollo (CIRAD), Ethiopian Institute of Agricultural Research, Jimma Agricultural Research Center (JARC), Institute of Biodiversity Conservation, Instituto Agronômico do Paraná (IAPAR), and Instituto Agronômico de Campinas (IAC). Those institutes enable the acquisition, exchange, conservation, duplication, and documentation of this crop’s valuable genetic resources, aiming the world food security. These organizations also performs phenotypic, cytogenetic, and molecular evaluation seeking elite accessions looking for specific attractive traits, primarily due to the already known low variability of Coffea arabica species, allowing in this way, putative well successful crosses.
The genebanks around the world have a collection of C. arabica which stands out with the most significant number of accessions (11,415), immediately succeeded by C. canephora (625), C. liberica (94), C. eugenioides (81) and other Coffea species (7756) [31].
CNRA was founded in 1998 and headquartered in Abidjan, Ivory Coast. According to Labouisse [13], CNRA has the most extensive genebank field collection of coffee in the world with 8003 accessions that resulted of prospecting conducted in eight African countries: Cote d’Ivoire, Guinea, Cameroon, Tanzania, Kenya, Madagascar and the Democratic Republic of the Congo.
Currently, the United States Department of Agriculture (USDA) comes again developing a Coffea collection as part of the National Plant Germplasm System, with approximately 300 accessions. In the past, this governmental department used to maintain 500 accessions of arabica coffee [31, 51].
Established in 1942, CATIE botanical garden and germplasm collection inaugurated its headquarter in Turrialba, Costa Rica. In 1948, the field collections of rubber, cocoa and coffee launched the germplasm preservation in Turrialba [52]. The CATIE International Coffee Germplasm Center is one organization in the public domain because of its designation to the International Institute ex-situ collections network under the auspices of FAO [3]. Their field genebank of coffee places the third in the world [52], and include to an ample range the entire genetic diversity of C. arabica recording 1987 accessions and above 9000 coffee trees. Also, the genetic diversity of a couple of other Coffea species is represented to a minor extent, covering 68 introductions of C. canephora and 24 introductions of C. liberica [49]. The C. arabica germplasm bank of CATIE possess 880 wild and semi-wild genotypes, 581 accessions of them acquired from collecting expedition performed by FAO and ORSTOM in Ethiopia - the known biodiversity hotspots; 923 belongs cultivars, mutants and selections section; 19 interspecific hybrids; and 165 intraspecific hybrids [3]. Considering that field collections maintenance is very costly to maintain, and the conserved genetic material is continuously endangered to biotic and abiotic stress, the research team of CATIE, from this point of view, developed a methodology for cryopreservation in liquid Nitrogen for long-term germplasm conservation of coffee seeds. Lately, CATIE maintains a core subset of 63 accessions from Ethiopia cryopreserved and thus establishing the first world cryobank [3, 53].
CIRAD commenced does collecting mission since the 1960s, being some of these collecting expeditions occurred in association with other institutions - viz., ORSTOM, International Plant Genetic Resources Institute (IPGRI), and IRD [3]. In 1977, an ORSTOM/CIRAD mission arrived in Kenya where they collected eighty different accessions of C. arabica at Mount Marsabitan, along with samples of C. eugenioides, C. zanguebariae, and C. fadenii. Subsequently, in 1989, samples from coffee plantation arising from 22 different origins were collected by an IPGRI/CIRAD mission-focused in Yemen. Besides that, the mission recognized six morphologically different types of coffee plants [3]. According to FAO-WIEW database 1990–2001, CIRAD maintain in Guyana a total 3800 accession ex-situ of coffee [31].
In Ethiopia, the Jimma Agricultural Research Center (JARC) has the commitment to be a leading centre of excellence research for arabica coffee on the planet, operating ten research stations located strategically in the main coffee production areas. The Jimma Research Station initiated variety development and germplasm conservation activity in 1966–1967. From 1966 to nowadays, the field collection has assembled 5853 accessions of C. arabica grouped in the following program/type: National collection - 1431, Exotic collection - 78, Coffee Berry Disease (CBD) resistance collection - 825, and Local landrace - 3519. To date, JARC has launched 42 coffee varieties. In Ethiopia, JARC is the unique public institution that has taken the initiative of multiplying and providing basic coffee seeds, primarily, coffee adapted varieties and CBD resistant material. Furthermore, this research institute plays a considerable role in dissemination and adoption of improved coffee technologies by innovative farmers, private and state-owned farms throughout the countryside [13, 54, 55]. Other important genetic resources organization in Ethiopia is the Institute of Biodiversity Conservation established in Choche (Limu) field genebank with 5196 accessions conserved [13].
In Brazil, the IAPAR was founded in 1972 and headquartered in Londrina, in the state of Paraná. The IAPAR operates in a 300 ha-farm, of which 40 ha are cultivated with coffee. In 1975 was established the field genebank of coffee that were primarily composed by IAC accessions with posterior inclusions of accessions from the FAO/IBPGR collection. Also, they have a partnership with five farmers to test the F3/F4 generations. Several cultivars have been released by IAPAR improved to achieve high yield, drought tolerance, resistance to rust, nematodes, bacterial blight, and leaf miner; and also, different ripening cycles. The IAPAR combine testing, seed production and demonstration to farmers in the F6 generation, speeding, in this way, the time to release genetic material. The IAPAR institution has a good reputation among of coffee farmer’s producers in Paraná [31].
The Instituto Agronômico de Campinas (IAC), institution of the Brazilian Coffee Consortium, maintains the largest and the oldest coffee germplasm bank in the country, with 5451 records. Supported by the framework of this diversity, the active germplasm bank of the “Instituto Agronômico” has contributed for 87 years with significant results in the Brazilian coffee research. IAC also perform a series of research in collaboration with other research institutions within the Brazilian Coffee Consortium [50, 56].
IAC continuously performs morphological, agronomic, chemical and molecular characterization of the genetic materials maintained in its germplasm banks. This is essential for the definition and identification of the most genetic promising materials, with better productivity and other attributes considered according to each survey. To achieve an desired coffee cultivar is required a long-term due to the time demanded to advance the genetic material from generation to generation. In Brazil, the two most adopted cultivars in coffee plantations, Mundo Novo and Catuaí, are the results of improvement research conducted by the “Instituto Agronômico” from its germplasm bank. They are planted in about 80% of Brazilian coffee crops area today [56].
Besides, the germplasm bank of the IAPAR and IAC, there are other five coffee germplasm banks in Brazil: Empresa de Pesquisa Agropecuária de Minas Gerais (EPAMIG), Universidade Federal de Viçosa (UFV), Instituto Capixaba de Pesquisa, Assistência Técnica e Extensão Rural (INCAPER), Fundação Procafé, and Embrapa Rondônia. According to Bramel [31], the collection of these germplasm banks has an estimation of about 13,856 accessions; however, the number of accessions may be inconsistent across reports.
As stated by Bramel [31], it is estimated 21,026 accessions in a compilation of world coffee collections that account 52 holding coffee germplasm collection with at least ten accessions.
5. Breeding and genetic diversity based on morphological and agronomic traits
In plant breeding, it is crucial to identify the most critical phenotypic traits to boost plant production. Consequently, the evaluation of trait occurrences and differences in a population is a key to determining probably valuable crosses among accessions. Although most studies focus on genetic diversity with molecular markers, it is also useful for plant breeders to recognize the morphological diversity of traits of interest [57].
Around the world, the arabica breeding programmes has the primary purpose of developing new cultivars taking into account the economic benefits to be returned to coffee growers. The target characteristics in the desired arabica cultivar are productivity, mainly focused on bean size as well as cup quality and resistance to major diseases and pests. On the other hand, each breeding programme has its own particularities that establish the priorities of selection criteria usually defined based on multifactorial variations in specific circumstances of weather conditions, soil, biotic and abiotic stresses, cropping systems, socio-economic factors, market dynamics and consumer preferences. In arabica coffee, typically, four primary methods of breeding and selection are used: 1- Pure line selection; 2- Pedigree selection after hybridization (sometimes also backcrossing); 3 - Intraspecific F1 hybrids; 4 - Interspecific hybridization (arabica x robusta), backcrossing and pedigree selection. The comprehensive overview of selection criteria and outcomes from each breeding method is presented in detail by Van der Vossen [58].
Gathering a series of studies, Monge and Guevara [52] make the compilation of the critical phenotypic markers for evaluation of coffee and suggests a list of appropriated traits evaluation markers: morphological descriptors - viz.: architectural (ramification degree, number of internodes, and length of plagiotropic branches) and physical (dimensions and color of leaves, flowers and fruits, flush color, stem diameter, etc.); phenological descriptor (flowering dates, fructification cycle duration); ecological adaptation descriptors (altitude, dry or humid regions, resistance to pest and diseases); productive descriptors (productivity level and early or late flowering, and fruit set); technological descriptors (coffee quality, the weight of 100 beans, caracoli rate, etc).
Monge and Guevara [52] in a review also outlined a compilation result of two studies concerning the phenotypic evaluation of 300 wild C. arabica collected in eight Ethiopia area, those accessions were added into CATIE collections in 1985. It highlighted the high variability in fruit maturation length (ranging from 130 to 258 days), a caracoli rate (varying from 1 to 71%), size of leaves, internode length and bean size. Furthermore, there was a detected correlation concerning morphologic variables - viz.: the lower ramification of the tree, the bigger the leaves and the bean that produces.
Cilas et al. [59], in a study concerning genetic value prediction for C. arabica production through evaluation of morpho-agronomic traits, having the yield registered throughout the first four years of production. They concluded that better coffee yield may be increased by the addition of the medium level of heterozygosity, once the hybrid present immense superiority in comparison to the parental line. Furthermore, these authors also affirm that the prediction of yield may also be fully achieved by combining morphological traits, for instance, stem diameter, number of primary branches and tree height.
Bertrand et al. [60], addressing efforts towards sustainability, performed a study in three Central American countries comprising of 15 trials between 2000 to 2006 aiming to assess F1 hybrids of C. arabica in the agroforestry system (shade) compared to full-sun (unshade) crop system. The experiment involved thirteen lines and twenty-one F1 hybrids that were measured to average production throughout the first production cycle earlier than pruning and coppicing. The results point out that the green coffee per tree yield was higher among F1 hybrids in contrast to traditional cultivar in 58%, aggregating to 170 g in agroforestry, whereas in the full-sun system this increment was 34%, accumulating 190 g. In this respect, the economic outcomes of both systems look quite similar. This study also discussed the economic advantage in the agroforestry system renovation with hybrids, indicating that after six years of replacing the traditional cultivar by hybrids could earn up 5000 USD/ha. They were also pointing to the facilitation of credit policies and the opportunity of reaching new market niches with differentiated prices.
The first original phenotypic structure within C. arabica was present by Montagnon and Bouharmont [61]. The authors observed eighteen morphological and agronomic characteristics in a field collection of 148 accessions used the analyzed by multivariate approach. Interestingly, the result allowed identifying a sharp structure split into two main groups, comprise respectively 53 and 76 accessions. The other six groups are composed of less than five entries. The principal component analysis explained 77% of the accumulated variation within the first two axes, which is reasonably good. Also, the authors believe that the arrangement of the two main structured groups combined with the historical evidence of those accessions infers that group 1 has not been engaged within the domestication pathway of C. arabica. The traits modified by the course of domestication partly explained the well-defined separation of those two main groups.
The genetic diversity study conduced in Tepi National Spices Agricultural Research Center on 93 C. arabica accessions based 22 quantitative characteristics was able to detect five clusters by using multivariate techniques of hierarchical cluster and principal component analysis [62]. According to Klief [62], the significant inter-cluster distances between clusters point out that there is a high probability for obtaining transgressive segregates and maximize heterosis by crossing germplasm accessions across distinct clusters.
An study carried out in southwestern Saudi Arabia evaluated the genetic variation of accessions of C. arabica conserved in-situ in 19 localities, where stressful conditions prevail. Multivariate approach applied on 17 quantitative traits detected five groups. Interestingly, four accessions from the same place were grouped in four different clusters, supporting the importance of in-situ conservation strategy. All cluster showed significant inter-cluster distance, where two clusters present highest cluster distance. Therefore, Tounekti et al. [63] affirms that from these findings, it is suitable to explore this variability in breeding programmes to overcome environmental stresses.
The biochemical aspect of coffee liquor is highly essential. From this point of view, it was made a study addressing the genetic diversity based on caffeine content level concurrently with physical aspects of green bean characteristics and coffee cup quality. The examination of dissimilarities involved cluster analysis based on unweighted pair group arithmetic average (UPGMA), together with correlation among those variables analyzed. The outcome results consisted of two main groups were distinguished. The first cluster formed by 11 accessions distinguished by high caffeine content, undesirable physical characteristics of green bean and poor coffee cup quality. The other cluster split into two subgroups: the first with 26 accessions with caffeine content varying from low to average level and cup quality; the next subgroup with five accessions characterized by a medium level of caffeine content, desirable physical qualities of green coffee bean and high-grade cup quality. The authors also identify negative and significant associations linking caffeine content and all other variables related to cup quality. From that perspective, it is possible a simultaneous improvement of desirable cup quality plus low caffeine content [64].
A research, performed in IAC, evaluated the effectiveness of a minimum set of descriptors established for the conduct of test for distinctness, uniformity and stability in C. arabica. Twenty-nine cultivars were scattered in 11 groups when assessed by 35 morphological characteristics and three agronomic traits during three years. The results demonstrate that those descriptors were skilled in discriminating cultivar groups but a minor role in the identification of cultivars within each group. Therefore, the authors recommend the adoption of molecular markers and biochemical descriptors to identify cultivars to be protected more accurately [65].
Weldemichael et al. [66] conducted one well-designed study estimating genetic parameters in 49 accessions of C. arabica. It was used 26 carefully chosen appropriated quantitative traits aiming to estimate the phenotypic variation. The statistical analyses approach consisted of a series of adequate genetic parameters estimation. The findings exhibited the occurrence of variability for some morphological traits among coffee germplasm accessions. Interestingly, coffee berry disease recorded a pronounced genetic gain per population mean (88.8%); this point draws particular attention, once in arabica coffee disease resistance is a breeding objective of the chief priority to plant breeders. The detected low genetic advance as per cent mean and/or low genotypic coefficients of variation exhibited in most traits indicating these characteristics could not be developed through simple section rather heterosis breeding. Conversely, they advise that high morphological variation is not a guarantee of pronounced genetic variation; in this viewpoint, it is helpful to take into consideration the molecular and biochemical studies as a complementary approach.
6. Genetic diversity based on molecular markers
The progress achieved in plant breeding programmes culminated in reduced genetic variability in the improved populations [36, 67, 68, 69]. This problem may be worse in species with a narrow genetic base, such as Arabica coffee (C. arabica). The narrow genetic base of this species is associated with its autogamy, the low number of plants that were initially distributed worldwide, and the recent evolution of the species [30, 36, 70]. Thus, genotype discrimination based on differences in phenotypic characteristics may be difficult because individuals who are genetically distinct may be phenotypically similar, which reduces the selective efficiency. To overcome this difficulty, molecular markers have been used as an important tool in the accurate discrimination of genotypes [71, 72].
DNA markers allow the detection of variations in DNA sequences between individuals of the same species. Because they identify variations in DNA, they are stable and are unaffected by the environment or by pleiotropic or epistatic effects [73]. Thus, molecular markers have been used in breeding programmes as an efficient tool for the discrimination of genotypes and the analysis of genetic variability, as their analysis is a precise association strategy between phenotypic and genotypic variability.
Genetic diversity assisted by molecular markers has been used in several stages of Arabica coffee breeding programmes. The molecular characterization of coffee accessions is an accurate tool for the conservation and more efficient use of genetic resources by breeders. This molecular information is useful in evaluating the redundancies and deficiencies of the germplasm and generates information on the efficiency of the collection, maintenance, and expansion of a germplasm bank. In addition, the study of molecular diversity provides fundamental information to help breeders choose parents to integrate into cross-breeding schemes, as well as in directing the improvement of the genetic base during the course of a breeding programme.
Different molecular markers, such as simple sequence repeats (SSRs), sequence-characterized amplified regions (SCARs), and single-nucleotide polymorphisms (SNPs), have been identified and made available for coffee [71, 72, 74, 75, 76, 77, 78, 79, 80, 81, 82]. These species-specific markers combined with random markers, such as inter-simple sequence repeats (ISSRs), random amplified polymorphic DNA (RAPD) and amplified fragment length polymorphisms (AFLPs); support the genetic breeding of this crop.
Genetic studies and analyses of diversity and molecular characterizations of different germplasm banks and cultivars of C. arabica have benefited from molecular marker technology. Coffee plants belonging to the group of the Híbrido de Timor (HdT) from the Brazilian germplasm bank of the Universidade Federal de Viçosa (UFV) in partnership with Empresa de Pesquisa Agropecuária de Minas Gerais (EPAMIG) and Empresa Brasileira de Pesquisa Agropecuária (Embrapa Café) have been studied in detail using AFLP and SSR markers [83]. HdT coffee plants are the result of natural hybridization between C. arabica and C. canephora and are one of the main sources of resistance genes to coffee diseases and pests [84, 85, 86]. Through molecular markers, redundancy was observed in the core collection of the HdT, so that two plants with different identifications corresponded to the same genotype. One of them was eliminated, resulting in a core collection containing 151 unique and properly discriminated HdTs. The data obtained allowed fingerprinting of the accessions [83]. The fingerprinting of each genotype allows the identification of individuals through a unique code. This information will provide reliability to breeders for germplasm maintenance, preservation, and exchange.
With 52 alleles from 22 SSRs, it was possible to access the diversity of the Core Collection of HdT [83]. Considerable variability was observed between the accessions, which were separated into 21 groups. This grouping result was analyzed together with the resistance data obtained for the main coffee diseases, rust and coffee berry disease. The concentration of individuals resistant to both diseases was verified in eight groups. Through this analysis, it was possible to identify HdT coffee plants belonging to distinct genetic diversity groups that have not yet been used in genetic breeding. This made it possible to select genotypes in the obtained dendrogram that were as distinct as possible from the sources already explored to date and that have different disease resistance genes. The selected HdT accessions consist of potential parents for breeding aiming resistance to multiple diseases [83].
Molecular markers were also analyzed in the HdT to understand the introgression of the genomes from the coffee species of their origin (C. arabica and C. canephora), as well as their potential impact on the cup quality on the C. arabica cultivars. HdT has the largest portion of the genome corresponding to C. arabica [87]; however, the small portion of C. canephora provides disease resistance genes. This portion, even though small, raises concern about the possibility of C. canephora affect the cup quality, since the beverage quality of C. canephora is known to be lower. Thus, the effect of introgression of C. canephora on HdT derivatives were evaluated [88, 89]. The study also demonstrated the presence of disease-resistant genotypes combined with good cup quality typical of C. arabica cultivars. The genetic diversity analysis showed high genetic similarity between HdT with C. arabica and clear differentiation among coffee species. The introgression of C. canephora in the HdT accessions did not reach 30%. The sensory analysis of the coffee genotypes showed no significant difference in the beverage quality parameters between C. arabica cv. Bourbon and HdT-derived cultivars, which demonstrated the possibility of developing C. arabica cultivars without affecting beverage quality [89].
Accessions of different species and interspecific hybrids from the germplasm bank of UFV/EPAMIG/Embrapa were also analyzed with genomic SSRs and expressed sequence tag–SSR markers. The combination of these two types of markers allowed discriminating all accessions, including genotypes traditionally of C. arabica, genotypes containing introgression of HdT, C. canephora, HdT, C. racemosa, and triploids of C. arabica and C. racemosa. This study also identified unique alleles that are useful for accession discriminating in breeding programmes and for cultivar fingerprinting [90, 91].
Using the currently available large-scale genotyping technology, genetic diversity between and within Brazilian coffee breeding progenies was assessed by 49,567 SNPs. The significant number of SNP molecular markers distributed throughout C. arabica genome was efficient in discriminating all evaluated accessions by grouping them according to their genealogies. Mixtures within the families were identified. New parents to be introduced in the ongoing breeding were identified, and the parents currently used were analyzed in detail. The population structure and its effect on obtaining the improved varieties of C. arabica were discussed [72].
Accessions from the germplasm bank and cultivars launched by the breeding programme of the Instituto Agronômico de Campinas were analyzed with RAPD, AFLP, and SSR markers [92]. The variability observed between accessions was small, and only two groups were formed, one containing genotypes that included most cultivars and the other containing accessions/cultivars derived from interspecific crosses.
A more comprehensive analysis of Brazilian coffee plants was performed in 34 cultivars belonging to the Brazilian Cultivar Trial, using SSR markers [93]. The molecular pattern obtained allowed the discrimination of all cultivars and the creation of a fingerprinting data of the main cultivars of the country. The ability of markers to detect varietal mixtures and the diversity between and within cultivars was demonstrated.
The genetic variability of C. arabica accessions from other countries, such as Costa Rica [94], Mexico [95], Nicaragua [96], India [97, 98, 99], Indonesia [100], China [101], Kenya [102] and Ethiopia [34, 103, 104, 105], has also been analyzed using markers such as ISSRs, SSRs, sequence-related amplified polymorphisms (SRAPs), AFLPs, and SNPs. In Ethiopia, different studies have shown the presence of great genetic variability in coffee plants. This variability has been attributed to the particular ecological characteristics of the country, such as its rainfall amplitude and its different altitudes, temperatures, and soil fertility, which are suitable for the crop. The presence of indigenous coffee production methods in the country has also contributed to this diversity [5, 106]. Greater genetic diversity has been reported among wild coffee populations than cultivated genotypes [103].
A broader study of the diversity and fingerprinting of Arabica coffee accessions from various producing regions of the world was done in 2533 genotypes [107]. These genotypes corresponding to the Core Collection of the germplasm of the Tropical Agricultural Research and Higher Education Center, accessions from Southern Sudan, and cultivars/germplasm from North, Central, and South America as well as Africa and Asia. The obtained fingerprinting was efficient. Based on this tool, farmers can verify and trust the identity of the cultivars being planted, and coffee roasters can rely on marketing related to the cultivars they are growing and selling. The seed and nursery sector can become more professional and reliable by using this new monitoring tool to establish and verify the genetic purity of the seed and seedling stock.
Currently, SNP markers are using for genome-wide investigation [72, 82, 108]. In an original work of genome-wide association, candidate genes associated with lipids and diterpenes contents in C. arabica were identified [108]. This study detects the domestication and breeding process in C. arabica, pointing out the switch in allele frequency, revealing high allelic richness in wild accessions. In this regard, the identification of these candidate genes outlining potential targets for improving beverage cup quality in a coffee breeding programme.
7. Conclusion
Genetic resources commendably provide the basis of genetics solution to solve numerous problems of coffee growing areas throughout the world. The experimental schemes that lead to the introgression of new agronomic traits are known and have previously been validated with large populations. This approach has allowed the combination of several desirable traits in a single coffee cultivar. Also, plant breeders currently can count on the employment of molecular genetics to enhance the competence to introduce the desirable characteristics in the new cultivar. Molecular marker approach in association with morpho-agronomic characterization and diversity study helps to efficiently maintain the germplasm bank and facilitated its use by the breeder. Molecular tools are also useful to detect genetic structure and divergent breeding subpopulation. Application of genomics as a supplementary approach to conventional coffee breeding is highly recommended, improve the productivity of the breeding programme by reducing time to variety development as well as assure selection of desirable traits on the course of the breeding process, this is specifically relevant for the coffee crop that is perennial and has a narrow genetic base. Furthermore, molecular and morphological diversity approach provides nurseries, farmers and the whole coffee industry an opportunity to increase knowledge about the genetic identity of the coffee tree planted or traded.
The highly-regarded line of attack in the coffee sector is the elaboration of a wide-ranging catalog on existing germplasm collections including the markers profile. In the world, the usage of genetic diversity available in germplasm collections faces two significant problems: limited access to the conserved genetic resources and the deficiencies of genetic evaluation. Anthropogenic disturbances have modified the natural habitats where wild coffee species have spontaneously evolved, and in consequence, much relevant germplasm is in the risk of destruction. So, efforts of the scientific community are essential to design and implement conservation strategies. The ongoing partnership between Latin America and the African countries involved in the conservation and evaluation of coffee genetic resources is a well-intentioned strategy. This network aims to revitalize and advance the research to boost the productivity and cup quality of the coffee.
Conflict of interest
The authors do not have conflict of interests.
\n',keywords:"economic importance, genetic resources, molecular markers",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/74239.pdf",chapterXML:"https://mts.intechopen.com/source/xml/74239.xml",downloadPdfUrl:"/chapter/pdf-download/74239",previewPdfUrl:"/chapter/pdf-preview/74239",totalDownloads:564,totalViews:0,totalCrossrefCites:0,dateSubmitted:"June 17th 2020",dateReviewed:"October 26th 2020",datePrePublished:"November 28th 2020",datePublished:"May 19th 2021",dateFinished:"November 28th 2020",readingETA:"0",abstract:"Coffea arabica L. is a native coffee species probably originated in Abyssinia, now Ethiopia. The genetic diversity of C. arabica has economic implications directly related to profits by breeding for developing new varieties to a global market. The economic value of C. arabica genetic resources are estimated at US$ 420 million, considered a 10% discount rate. Understanding the extent of traits variability and genetic diversity is essential to guide crosses between genotypes, targeting the development of new varieties with high economic value. This chapter will present the C. arabica economic importance, primarily to Brazil, the most significant world producer; we will outline the origin and dispersion of arabica coffee and briefly show the leading germplasm banks. We will also point out contribution of genetic diversity studies based on morphological, agronomic traits, and molecular markers supporting the development of new varieties. Finally, we present an outline for the future.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/74239",risUrl:"/chapter/ris/74239",signatures:"Juliano Lino Ferreira, Eveline Teixeira Caixeta, Fernanda Fatima Caniato, Tesfahun Setotaw, Gustavo César Sant’Ana and Leila Maria Ferreira",book:{id:"9743",type:"book",title:"Genetic Variation",subtitle:null,fullTitle:"Genetic Variation",slug:"genetic-variation",publishedDate:"May 19th 2021",bookSignature:"Rafael Trindade Maia and Magnólia de Araújo Campos",coverURL:"https://cdn.intechopen.com/books/images_new/9743.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83881-097-9",printIsbn:"978-1-83881-096-2",pdfIsbn:"978-1-83881-101-3",isAvailableForWebshopOrdering:!0,editors:[{id:"212393",title:"Prof.",name:"Rafael",middleName:"Trindade",surname:"Trindade Maia",slug:"rafael-trindade-maia",fullName:"Rafael Trindade Maia"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"87534",title:"Dr.",name:"Juliano",middleName:"Lino",surname:"Ferreira",fullName:"Juliano Ferreira",slug:"juliano-ferreira",email:"julianolf@yahoo.com.br",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/87534/images/2505_n.jpg",institution:{name:"Brazilian Agricultural Research Corporation",institutionURL:null,country:{name:"Brazil"}}},{id:"110703",title:"Dr.",name:"Tesfahun Alemu",middleName:null,surname:"Setotaw",fullName:"Tesfahun Alemu Setotaw",slug:"tesfahun-alemu-setotaw",email:"setotaw2006@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Empresa de Pesquisa Agropecuária de Minas Gerais",institutionURL:null,country:{name:"Brazil"}}},{id:"275651",title:"MSc.",name:"Leila",middleName:null,surname:"Ferreira",fullName:"Leila Ferreira",slug:"leila-ferreira",email:"leilamaria2003@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"324835",title:"Dr.",name:"Eveline",middleName:null,surname:"Teixeira Caixeta",fullName:"Eveline Teixeira Caixeta",slug:"eveline-teixeira-caixeta",email:"eveline.caixeta@embrapa.br",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"324838",title:"Dr.",name:"Fernanda Fátima",middleName:null,surname:"Caniato",fullName:"Fernanda Fátima Caniato",slug:"fernanda-fatima-caniato",email:"fernanda_f_caniato@ufam.edu.br",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"336511",title:"Dr.",name:"Gustavo César",middleName:null,surname:"Sant'Ana",fullName:"Gustavo César Sant'Ana",slug:"gustavo-cesar-sant'ana",email:"gustavosantana@tmg.agr.br",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Economic importance of Coffea arabica",level:"1"},{id:"sec_3",title:"3. Origin and distribution of Coffea arabica",level:"1"},{id:"sec_4",title:"4. Coffea arabica genetic resources",level:"1"},{id:"sec_5",title:"5. Breeding and genetic diversity based on morphological and agronomic traits",level:"1"},{id:"sec_6",title:"6. Genetic diversity based on molecular markers",level:"1"},{id:"sec_7",title:"7. Conclusion",level:"1"},{id:"sec_11",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Morris J. Coffee: A Global History. 1st ed. London: Reaktions Books; 2018. 176 p'},{id:"B2",body:'Zhou L, Vega FE, Tan H, Lluch AER, Meinhardt LW, Fang W, et al. Developing Single Nucleotide Polymorphism (SNP) Markers for the Identification of Coffee Germplasm. Trop Plant Biol. 2016;9:82-95. DOI: 10.1007/s12042-016-9167-2'},{id:"B3",body:'Vega FE, Ebert AW, Ming R. Coffee germplasm resources, genomics, and breeding. 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The Híbrido de Timor germplasm: identification of molecular diversity and resistance sources to coffee berry disease and leaf rust. Euphytica. 2018;214:153. DOI: 10.1007/s10681-018-2231-2'},{id:"B84",body:'Bettencourt, A.J.; Noronha-Wagner, M.; Lopes J. Factor genético que condiciona a resistência do clone 1343/269 (“Híbrido de Timor”) à Hemileia vastatrix Berk. & Br. Brotéria Genética. 1980;1:53-58'},{id:"B85",body:'Wallace, Gonçalves; Pereira AA. Resistência de cafeeiros a nematóides IV-reação de cafeeiros derivados de Híbridos de Timor a Meloidogyne exigua. Nematol Bras. 1998;22:39-50'},{id:"B86",body:'Pereira AA, Sakiyama NS, Zambolim L, Moura WM, Zambolim EM, Caixeta ET. Identification and use of sources of durable resistance to coffee leaf rust in the UFV/EPAMIG breeding program. In: Zambolim, L.; Zambolim, E.M.; Várzea VMP, editors. Durable resistance to coffee leaf rust. 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His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. 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In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. 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His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. from Integral University, Lucknow, India, with his work titled ‘Development and evaluation of silymarin nanoformulation for hepatic carcinoma’. Currently, he is an Assistant Professor of Pharmaceutics, at the Faculty of Pharmacy, Integral University. He has been teaching PharmD, BPharm, and MPharm students and conducting research in the novel drug delivery domain. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than twenty-four original journal articles, two edited books, four book chapters, and several scientific articles to his credit. He is a member of the American Association for Cancer Research, the International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}}]}},subseries:{item:{id:"25",type:"subseries",title:"Evolutionary Computation",keywords:"Genetic Algorithms, Genetic Programming, Evolutionary Programming, Evolution Strategies, Hybrid Algorithms, Bioinspired Metaheuristics, Ant Colony Optimization, Evolutionary Learning, Hyperparameter Optimization",scope:"Evolutionary computing is a paradigm that has grown dramatically in recent years. This group of bio-inspired metaheuristics solves multiple optimization problems by applying the metaphor of natural selection. It so far has solved problems such as resource allocation, routing, schedule planning, and engineering design. Moreover, in the field of machine learning, evolutionary computation has carved out a significant niche both in the generation of learning models and in the automatic design and optimization of hyperparameters in deep learning models. This collection aims to include quality volumes on various topics related to evolutionary algorithms and, alternatively, other metaheuristics of interest inspired by nature. 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Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. 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Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/142082",hash:"",query:{},params:{id:"142082"},fullPath:"/profiles/142082",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()