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Chaoyang Zhang, Hai Xie, Yiting Yang, Qian Yang, Haibin Tian, Lixia Lu, Weiye Li, Jingfa Zhang, Guo-Tong Xu; Erythropoietin Protects Retinal Pigment Epithelium in Experimental Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5359.
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This study was to explore the possible protective mechanism(s) of EPO on retinal pigment epithelial cells (RPE) in diabetic rat retinas.
The Sprague-Dawley rats were rendered diabetes with intraperitoneal injection of streptozotocin, followed by intravitreal injection of EPO after 2 hours; 2 and 4 weeks later, the permeability of outer blood-retinal barrier was examined by using FITC-dextran leakage assay. The glyoxal-treated ARPE-19 cells, incubated with EPO or soluble EPO receptor, were studied for cell viability, barrier function, etc. The expressions of ZO-1, occludin, VEGFR2, HIF-1α, MAPKs and AKT were examined with Western blot and immunofluorescence.
The leakage of FITC-dextran was detected mainly in outer nuclear layer in 2-week diabetic rat retinas and became more obvious in 4-week diabetic rat retinas. The leakage was largely ameliorated in EPO-treated diabetic rats. The protein expressions of ZO-1 and occludin in the RPE-Bruch’s membrane choriocapillaris complex were decreased, while HIF-1α and JNK pathways were increased, significantly in 4-week diabetic rats, which were reversed by EPO treatment. The in vitro study with ARPE-19 cells also confirmed above changes and the protective effect of EPO.
EPO could protect RPE cells and maintain its barrier integrity through upregulation of ZO-1 and occludin in diabetic rats. The protective mechanism(s) of EPO might be through its downregulation of HIF-1α and JNK pathways, thus protecting outer blood-retinal barrier.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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