The renin-angiotensin system (RAS) plays an important role in the pathogenesis of inflammation and autoimmune dysfunction. Uveitis is a sight-threatening intraocular inflammatory disorder caused by infectious agents, autoimmune mechanisms, exposure to toxins and many other unknown factors. Most components of RAS have been identified in every organ including the eye. The tissue-specific RAS is believed to exert diverse physiological effects locally independent of circulating angiotensin II (AT II) which functions as the effector arm of RAS causing potent proinflammatory responses via Angiotensin type 1 receptor (AT1R). AT II mediated stimulation of tissue factor (TF), the principal initiator of the clotting cascade and a major regulator of haemostasis and thrombosis rapidly inducible by inflammatory agents in several cell lines including monocytes. Activation of NFκB, a key redox-sensitive transcription factor encoding for the TF gene, plays a key role in that mechanism amplified by locally synthesized angiotensin I. (AT I) The second arm of RAS establishes systemic and local protective axis against inflammation and autoimmune dysfunction via angiotensin-converting enzyme 2 (ACE2) which is a zinc-metallopeptidase able to cleave AT II to form angiotensin-(1–7) [AT-(1–7)]. AT-(1–7), a biologically active peptide, binds to a G-protein coupled receptor Mas, and activates signaling pathways that counteract the effects of AT II by negatively effecting inflammatory responses and negatively modulating leukocyte migration, cytokine expression and release, and fibrogenic pathways. The purpose of this chapter is to analyze both pro-inflammatory and protective role of RAS in ocular inflammation and uveitis both in humans and experimental models.
Part of the book: Renin-Angiotensin System