The extraocular muscles are highly specialized muscles responsible for the complex movements of the eyeball. They differ from other skeletal muscles in many respects, including fundamental components of the contractile apparatus and the extracellular matrix. Using immunohistochemistry and a battery of well-characterized antibodies, we have investigated the composition of the cytoskeleton of their myofibers with respect to desmin, vimentin, and nestin. In the adult and fetal human extraocular muscles, a subgroup of the slow tonic muscle fibers is lacking desmin. These fibers, which are multiply innervated, show a normal myofibrillar arrangement, maintained mitochondrial distribution, and sarcolemma integrity. Desmin, the most abundant intermediate filament protein in muscle, has been considered a ubiquitous protein in skeletal muscle fibers where it links adjacent myofibrils and the myofibrillar network to the sarcolemma, the mitochondria and the membrane of the nuclei. The functional implications of the lack of desmin remain to be determined, but these findings represent a paradigm shift, as desmin has been regarded a ubiquitous protein of the cytoskeleton of muscle fibers.
Part of the book: Cytoskeleton
The extraocular muscles differ from other skeletal muscles in many respects but most strikingly in their response to neuromuscular diseases expected to affect the whole body. Oculomotor disturbances are not typical features of ALS. Recent data ascribe the muscle tissue an important role in the pathophysiology of ALS, with early involvement of the neuromuscular junctions and loss of axonal contact. We show that the extraocular muscles of terminal ALS donors and also of mice models of ALS maintain their morphology and well-preserved neuromuscular junctions until the end stages of the disease, whereas the limb muscles are severely affected and their neuromuscular junctions start losing contact with the supplying axons early in the course of ALS. There are intrinsic differences between the extraocular and limb muscles with respect to neurotrophic factors and Wnt isoforms and fundamental differences in their response to ALS that cannot be explained by the aging process. We propose that these differences may be instrumental in the selective sparing of the extraocular muscles in ALS.