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F. Pedrosa Domellof, T. Brännström, P. Andersen, S. Marklund, J.-X. Liu; Nerve-Muscle Interplay in the EOMs: Effects of Progressive Denervation on Human and Transgenic Mice With Amyotrophic Lateral Sclerosis (ALS). Invest. Ophthalmol. Vis. Sci. 2009;50(13):3038.
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© ARVO (1962-2015); The Authors (2016-present)
To explore extent and consequences of progressive denervation in the EOMs of ALS patients and of transgenic ALS mouse models.
EOM samples obtained at autopsy from 7 ALS patients and from 4 elderly controls (72-86 y), 7 adult controls (26-56 y), as well as from transgenic mice with SOD1 mutations (D90A, G93A, G85R) paralleling familiar ALS, were processed for immunocytochemistry with antibodies against Schwann cell markers (S-100, p75, GFAP), gangliosides GD1b and GQ1b/GT1a, parvalbulmin, myosin heavy chains and laminin chains. Neuromuscular junctions (NMJs) were identified with alpha-bungarotoxin and acetylcholinesterase.
Differences in the expression of gangliosides GD1b and GQ1b/GT1a and Schwann cell marker S-100 at the NMJs and nerves were noted in the human EOMs of ALS patients compared to those of the elderly controls. Parvalbumin was absent or scarce in EOM nerve trunks of ALS patients, with few exceptions. Changes in the composition of the extracellular matrix observed in EOMs of human familial ALS with D90A mutation were also present in the corresponding transgenic mouse. Further characterization of the EOMs in the transgenic mice is ongoing.
There are signs of denervation of the human EOMs in late stages of ALS although these muscles appear selectively spared at the muscle fiber level. The presence of high levels of parvalbumin have been proposed to be protective for oculomotor neurons in ALS but in advanced stages of the disease this difference in calcium-binding proteins is no longer apparent in most cases. The identification of similar endpoints in the EOMs of patients with D90A mutation and the ALS transgenic mice carrying the same mutation indicates that this is a useful model to study the temporal aspects of progressive denervation in the EOMs and to explore aspects of muscle-nerve interplay that protect the EOMs in motoneuron disease. Finally knowledge on the effects of denervation may give us insights on the spatial organisation of motor units and fascicle organisation in the EOMs.
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