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Zara Mehrabyan, Yan Guo, Steven Bernstein; Time course of oligodendrocyte death after rAION in Sprague Dawley rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1422.
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Nonarteritic anterior ischemic optic neuropathy (NAION) is an optic nerve (ON) infarct, and the most common cause of sudden ON-related vision loss in individuals over 55 years of age. Previously we and others have shown after ON injury, RGC death peaks around 10 days post-insult and >90% complete by 21 days, but little is known about the time course of oligodendrocytes death following ON infarct. Since ON function can improve or decline long after NAION, this suggests that mechanisms other than primary RGC death may play important roles. We wanted to evaluate the timing of post-rAION apoptotic oligodendrocyte death correlating it with ON-immune and stress responses
rAION was induced (16 sec/50mW/500um spot/2.5mM/ml RB) in SD rats (n=3 nerves/time point). Animals were euthanized 0-40 days post-induction. 10 uM frozen sections were taken from 2mm behind the globe. Optic nerve cross sections were analyzed by TUNEL assay at times from 0-42 days post AION induction. We identified intact axons by SMI-312 neurofilament immunostaining. Inflammatory cells were identified using IBA-1 immunolocalization and stress transcription factor c FOS response was evaluated.
Post-rAION apoptotic oligodendrocyte death, measured by TUNEL staining, only begins after 7 days post-induction and doesn’t peak until 30d. Cell death is present even 42 days post-induction. Neurofillament identification reveals that there is localization of TUNEL (+) cells to the general areas of axonal damage.
RGC apoptosis occurs much earlier than oligodendrocytes. The oligodendrocyte response to sudden anterior ON ischemia is prolonged as compared with RGCs. The prolonged period of oligodendrocyte death suggests a potentially longer treatment time window for limiting post-infarct oligodendrocyte demyelination and death than for RGCs. It also means that, like RGC stereology, functional and cell death analyses for treatments designed to preserve ON function need to be evaluated at least one month after rAION induction.
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