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Steven L. Bernstein, Bernard J. Slater, Yan Guo, Yan Guo, Fernandino L. Vilson, Danny Weinreich; Post-NAION Demyelination: Treatment Targeting. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3163.
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Post-stroke demyelination is well known to occur in CNS infarcts, and recovery from this process may be important clinically. Post-NAION inflammation is a key component in NAION and its models (Salgado and Vilson et al, Arch. Ophth. 2011), and inflammatory modulation can play a role in ON damage and recovery (Nakazawa et al, J. Neurosci. 2006). We looked at post-infarct demyelination in models of nonarteritic anterior ischemic optic neuropathy (NAION), and evaluated whether modifying post-stroke inflammation is a useful target for enhancing post-NAION recovery.
We analyzed both primate and rodent ONs for demyelination immuno-histochemically following NAION model induction, and ultrastructurally using transmission electron microscopy (TEM). Real-time quantitative PCR (rq-PCR) was used to evaluate oligodendrocyte-associated gene expression. We evaluated rodent ON function by compound action potentials (CAPs) in isolated ON preps of control and infarcted ONs. The cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) was injected intraventricularly 3 days post-infarct induction, at the peak of inflammatory response.
TEM reveals that there was a considerable demyelinating component following rAION induction, This demyelination is in excess of axonal loss, and detectable immunohistochemically using the intra-neural difference between intact axons and oligodendrocytes. CAP analysis revealed a significant functional component of post-AION demyelination, which was reversible at 30 days post-stroke using GM-CSF.
Post-ischemic demyelination plays a significant role in NAION models, and likely in clinical NAION. The reversible portion of this phenomenon may contribute to the sizable number of patients that show clinical recovery following an episode of NAION. Agents such as GM-CSF directed at this mechanism may be useful in improving recovery from NAION, even when administered at times distant (>3 days) from the onset of the disease.
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