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DM Rosenbaum, AK Junk, M Singh, S Malhotra, A Mammis, S Roth, PS Rosenbaum; Erythropoietin Acts as an Endogenous Neuroprotective Agent in Retinal Ischemia . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1996.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The purpose of this study was to examine the role of erythropoietin (EPO)/erythropoietin receptor (EPOR) in a model of transient retinal ischemia. Methods: Transient retinal ischemia was induced in adult Sprague-Dawley rats by raising the intraocular pressure to 120 mm Hg. Immunohistochemistry and Western blotting were performed at different time points following reperfusion. In a separate set of experiments, exogenous EPO was administered either prior to or following ischemia and the degree of retinal damage was assessed by measuring the thicknesses of the retinal layers. Electrophysiology (ERG) was performed following ischemia to assess functional outcome. TUNEL staining was also performed to determine whether EPO treatment resulted in fewer TUNEL positive cells in the vulnerable inner retina. Finally, soluble EPOR was administered intravitreally prior to ischemia to determine its effect on outcome. Results: Immunohistochemistry demonstrated increased expression of the EPOR that was evident at 12 hours and peaked at 48-72 hours following 60 minutes of ischemia. EPOR expression co-localized with phenotype markers for retinal neurons and glial cells. Similarly, Western blot analysis demonstrated increased expression of the EPOR protein starting at 12 hours and peaking at 48-72 hours following ischemia. EPO (5000 U/kg) administered either 24 hours prior to or immediately following 45 minutes of ischemia resulted in significantly less decrease in the thickness of the inner retinal layers in those animals treated with EPO as compared to control animals when examined 7 days later. EPO treatment also resulted in preservation of the ERG-b wave at 7 days. There were fewer TUNEL positive cells at 24 hours following ischemia in the EPO-treated animals as compared to controls. The administration of soluble EPOR increased the extent of retinal damage when administered prior to ischemia as compared to vehicle-treated controls. Conclusion: These data demonstrate that the EPO-EPOR system may act as an endogenous neuroprotective system and that exogenous EPO may show promise as a potential neuroprotective agent in transient retinal ischemia.
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