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J.-X. Liu, F. Pedrosa-Domellof; Impact of Amyotrophic Lateral Sclerosis (ALS) on the Extracellular Matrix of Human Extraocular Muscles. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5826.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the laminin isoform composition of the basement membranes (BMs) in extraocular muscle fibers, intramuscular nerves, blood vessels, capillary and neuromuscular junctions (NMJs) in normal subjects and terminal ALS patients to survey the impact of ALS in the human EOMs.
EOM samples obtained at autopsy from 7 ALS patients and from 4 elderly controls (72-86 y) were processed for immunocytochemistry with monoclonal antibodies against laminin chains (Ln) α2, α4, α5, and β2. Neuromuscular junctions (NMJs) were identified with alpha-bungarotoxin.
The immunoreactivity with anti-Lnα2, -Lnβ2 and -Lnα5 decreased erratically in the extrasynaptic BM of EOM fibers from all patients except one whose fiber contours showed normal immunoreactivity with anti-Lnα2. Lnα4 was absent from the extrasynaptic BM of ALS EOMs. Over 1000 NMJs were examined. The majority of the NMJs did not contain Lnα2 (76.7%) or Lnβ2 (74%) but contained Lnα4 (78.9%) and Lnα5 (71.8%). The perineurium of intramuscular nerve bundles in ALS showed decreased Lnβ2. The endoneurium in ALS lacked Lnα2, α5 and β2 but had unchanged Lnα4. In most ALS muscle sections the capillaries showed normal Lnα4 and α5 but lacked Lnβ2.
In terminal stages of ALS, the BM of EOM fibers, their neuromuscular junctions, nerve fibers, blood vessels and capillaries showed altered laminin chain composition, although the EOMs are remarkably spared compared to the limb muscles of these patients. These changes in laminin composition were independently regulated for laminin chain isoform and tissue location, indicating a complex impact of ALS in the human EOMs.
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