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S. L. Bernstein, C. Chen, N. Miller, B. J. Slater, M. A. Johnson; A Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy (pNAION). Invest. Ophthalmol. Vis. Sci. 2007;48(13):4410.
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Nonarteritic anterior ischemic optic neuropathy (NAION) is the leading cause of sudden optic nerve-related vision loss, but little is known of the acute histology or pathophysiology of this disorder. We previously reported on the generation of rodent models of NAION (Bernstein et al, IOVS, 2003; Goldenberg-Cohen et al, IOVS, 2005). However, there are considerable differences between rodent and primate retinae and optic nerves, which make it difficult to accurately predict responses to neuroprotective strategies for optic nerve ischemia. We report on the generation of a primate model of NAION (pNAION).
Toxicological studies were performed prior to induction experiments. Male rhesus monkeys (4-6y/o; 6-7-5kg) were injected intravenously with rose Bengal (2.5mg/kg). A frequency doubled YAG laser (535nm) with a 1.4mm spot size was used to illuminate the optic disk, and generate superoxide radicals via dye activation. Blood was drawn prior to induction, and at varying times post-induction, and analyzed for standard clinical values, as well as inflammatory markers. Retinal photography was performed, as well as fluorescein angiography, pre-and post induction. Retinal and optic nerve electrophysiological measures (ERG, pattern ERG, and pattern VEP) were evaluated pre and post-induction at different times. Animals were euthanized and tissues obtained for histological analysis.
Rose Bengal did not shown significant toxicity at the doses used. While sham-induced eyes showed no visible changes, experimental eyes showed optic nerve edema, with IVFA-documented disk leakage at 1 week. Changes in pattern VEP and pattern ERG amplitudes in induced eyes were seen consistent with those observed in NAION. An afferent pupillary defect was seen in the affected eyes. Histologically, there is a loss of retinal ganglion cells and optic nerve/axonal loss, similar to that reported in human NAION.
A primate model of NAION (pNAION) has been successfully induced and closely resembles clinical NAION in many respects. The model is likely to be highly useful in closely evaluating the specific pathophysiological and genetic changes associated with human NAION. The model will also provide an excellent resource for evaluating neuroprotective strategies for optic nerve ischemia and white matter infarcts in general.
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