Open Access
Anti-VEGF effects of intravitreal erythropoietin in early diabetic retinopathy
Jingfa Zhang1,Liu-Mei Hu1,Guoxu Xu1,Yalan Wu1,Jianfeng Shen1,Yan Luo1,Yong Zhong1,Stephen H Sinclair1,Myron Yanoff1,Weiye Li1,Guo-Tong Xu1
Department of Regenerative Medicine, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China
DOI: 10.2741/E151 Volume 2 Issue 3, pp.912-927
Published: 01 June 2010
(This article belongs to the Special Issue Hyperspectral imaging in biomedicine)

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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Jingfa Zhang, Liu-Mei Hu, Guoxu Xu, Yalan Wu, Jianfeng Shen, Yan Luo, Yong Zhong, Stephen H Sinclair, Myron Yanoff, Weiye Li, Guo-Tong Xu. Anti-VEGF effects of intravitreal erythropoietin in early diabetic retinopathy. Frontiers in Bioscience-Elite. 2010. 2(3); 912-927.