IMR Press / FBE / Volume 2 / Issue 3 / DOI: 10.2741/E151

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Article
Anti-VEGF effects of intravitreal erythropoietin in early diabetic retinopathy
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1 Tongji Eye Institute and Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, China
2 Laboratory of Clinical Visual Sciences, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai JiaoTong University School of Medicine, Shanghai, China
3 Dept. of Ophthalmology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
4 Dept. of Ophthalmology, Second Affiliated Hospital of Soochow University, Suzhou, China
5 Dept. of Ophthalmology, Drexel University College of Medicine, Philadelphia, PA, USA
Front. Biosci. (Elite Ed) 2010, 2(3), 912–927; https://doi.org/10.2741/E151
Published: 1 June 2010
Abstract

In the present study, a single intravitreal erythropoietin (EPO) to diabetic rats produced therapeutic effects on blood-retinal barrier (BRB) function and neuronal survival at different time courses of retinopathy. In parallel, the hypoxia-inducible factor 1 alpha (HIF-1 alpha) pathway has been quantitatively studied, including VEGF-A, endogenous EPO, EPO receptor (EpoR), prolyl hydroxylases (PHD1-3) and von Hippel-Lindau tumor suppressor (VHL). The mRNA levels of HIF-1 alpha, VEGF-A, endogenous EPO, PHD1-3 and VHL are all up-regulated in the diabetic retina, and suppressed by exogenous EPO. The increased protein levels of HIF-1 alpha, VEGF-A, and endogenous EPO found in diabetic retinas also have been down-regulated by exogenous EPO. The results demonstrate that the HIF-1 pathway is activated in the retina in early diabetes, but is negatively regulated by a feedback loop following the administration of exogenous EPO. Exogenous EPO at pharmacologic levels leads to suppression of VEGF and in turn, restoration of the normal functions of BRB in a time-dependent manner. In the diabetic retina, the same level of exogenous EPO that inhibits VEGF also exerted neuronal protection.

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