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Yan Wang, Dale Brown, Brant Watson, Yuanli Duan, Jeffrey L. Goldberg; A Novel Rodent Model of Posterior Ischemic Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2977.
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Posterior Ischemic optic neuropathy (PION) is a sight devastating disease in clinical practice. However its pathogenesis and natural history has remained poorly understood. The purpose of this study was to develop a reliable, reproducible animal model of PION and test the treatment effect of neurotrophic factors on PION model.
PION was induced in adult Sprague-Dawley rats by illuminating the posterior portion of optic nerve with Nd:YAG laser immediately after intravenous injection of erythrosine B (EB). The integrity of the circulation in the retina and optic nerve was examined by FITC-dextran extravasation 1 hour after PION induction. The histopathologic and inflammatory changes of the optic nerve were characterized by H&E and ED1 immunostaining. RGC survival at different time points after PION induction, with or without neurotrophic application, was quantified by counting the number of Fluorogold retrograde-labeled RGCs in retina flat mounts.
Fluorescein dye leakage was observed in the lesion area of the optic nerve one hour after PION induction. The lesion area of the optic nerve became edematous 3 days post injury and then underwent cavernous degeneration. ED1 positive microglia/macrophages first appeared in the lesion area and migrated to the distal portion of optic nerve as well as optic chiasm. RGCs died in a time dependent manner and around 30% RGCs survived 3 weeks post injury. Multiple application of BDNF or CNTF, however, could rescue RGC survival up to 70% 3 weeks post injury.
The retinal and optic nerve changes occurring after PION induction were similar to key features of human PION. Our model provides a novel platform for future research on detailed pathogenesis and molecular changes in PION; and can be further optimized for pre-clinical drug screening of interventional agents against PION as well as other CNS ischemic disease.
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