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F. Pedrosa Domellof, M. Lindström, T. Brännström, P. M. Andersen, J.-X. Liu; Human Extraocular Muscles in Amyotrophic Lateral Sclerosis (ALS). Invest. Ophthalmol. Vis. Sci. 2008;49(13):4492. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To survey the EOMs of patients deceased with ALS, with respect to contractile proteins and extracelluar matrix (ECM) composition, satellite cell content, innervation and capillarisation, in order to evaluate the possible involvement of EOMs in this disease.
Eleven EOM samples obtained at autopsy from 4 ALS patients were processed for immunocytochemistry, with monoclonal antibodies against i) myosin heavy chains (MyHC slow-twitch, slow-tonic, fast-twitch, embryonic, α-cardiac and extraocular), ii) laminin chains (Ln) α1, α2, α4, α5 and β2, iii) Pax-7, N-CAM, MyoD and Myogenin. Hematoxylin and eosin, NADH-TR, acetylcholinesterase and alpha-bungarotoxin labeling were also used.
Wider variation in fiber diameter than normally seen in EOMs, including apparently atrophic and hypertrophic groups of fibers, was noted in 8 of 11 muscles. Although the distribution of fast and slow MyHC isoforms closely resembled those found in normal EOMs, MyHC embryonic was only present in sporadic fibers of most ALS muscles. The pattern of distribution of MyHC slow-tonic was also affected.In most ALS cases, Ln α2 was the only laminin isoform observed in the basement membrane of the EOM fibers, whereas Ln α4, α5 and β2 isoforms were lost. NMJs looked rather normal with acetylcholinesterase but strickingly lacked Ln β2. Ln α2 and β2 isoforms were also missing in perineurium and endoneurium and Ln α5 was absent in endoneurium. In capillary and blood vessels, Ln α4, α5 were maintained whereas Ln β2 was absent.Evaluation and quantification of satellite cells is ongoing.
These EOMs of patients deceased with ALS showed evidence of altered content of contractile proteins and structure-specific changes in the composition of the extracellular matrix. The altered Ln composition of the neuromuscular junctions and nerves is likely to be functionally relevant and the absence of MyHC slow tonic and embryonic may impart on the contractile properties of the fibers. Although EOMs and oculomotor system were formerly thought to be spared in ALS, oculomotor abnormalities have been recently reported in some patients with ALS. Further studies are underway to determine the functional implications of our findings.
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