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The extraocular muscles in Amyotrophic Lateral Sclerosis (ALS)?
Author(s) -
PEDROSA DOMELLOF F,
BRÄNNSTRÖM T,
ANDERSEN PM,
LIU JX
Publication year - 2008
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2008.4423.x
Subject(s) - amyotrophic lateral sclerosis , extraocular muscles , laminin , myosin , biology , gene isoform , anatomy , reinnervation , immunocytochemistry , endoneurium , chemistry , pathology , extracellular matrix , endocrinology , microbiology and biotechnology , medicine , biochemistry , sciatic nerve , disease , gene
Purpose To investigate the morphology, fiber type composition, contractile proteins, extracelluar matrix (ECM), innervation and capillarisation, of the extraocular muscles (EOM) of patients deceased with ALS, in order to evaluate the possible involvement of EOMs in this disease. Methods EOM and limb muscle samples obtained from 5 ALS patients and age matched controls at autopsy were processed for immunocytochemistry, with monoclonal antibodies against myosin heavy chain isoforms; laminin chains (Ln) α1, α2, α4, α5 and β2; etc. Hematoxylin and eosin, NADH‐TR, acetylcholinesterase and alpha‐bungarotoxin were also used. Results The EOMs of ALS patients appeared remarkably unaffected, in strong contrast to the limb muscles. Wider variation in fiber diameter than normally seen in EOMs, including apparently atrophic and hypertrophic groups of fibers, was noted. MyHC embryonic was only present in sporadic fibers and the pattern of distribution of MyHC slow‐tonic was also affected. In most ALS cases, Ln α4, α5 and β2 isoforms were lost from the basement membrane of the EOM fibers . The laminin content of the neuromuscular junctions was altered, Ln α2 and β2 isoforms were 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. Conclusion The changes observed in EOMs with ALS suggest that they are not completely spared in this motoneuron disease although they are significantly less affected that limb muscles. The altered contractile protein content and structure‐specific changes in the composition of the ECM are likely to be functionally relevant. Further studies are underway to determine the functional implications of our findings.