Anti-VEGF effects of intravitreal erythropoietin in early diabetic retinopathy.
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.
Department of Regenerative Medicine, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
Jingfa
J
Zhang
Liu-Mei
LM
Hu
Guoxu
G
Xu
Yalan
Y
Wu
Jianfeng
J
Shen
Yan
Y
Luo
Yong
Y
Zhong
Stephen H
SH
Sinclair
Myron
M
Yanoff
Weiye
W
Li
Guo-Tong
GT
Xu
D000818:Animals; D001483:Base Sequence; D001813:Blood-Retinal Barrier; D017931:DNA Primers; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D004921:Erythropoietin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020287:In Situ Nick-End Labeling; D008297:Male; D008854:Microscopy, Electron; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014822:Vitreous Body
D017931:DNA Primers; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin