Anti-VEGF effects of intravitreal erythropoietin in early diabetic retinopathy

Front Biosci (Elite Ed). 2010 Jun 1;2:912-27. doi: 10.2741/e151.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blood-Retinal Barrier
  • DNA Primers
  • Diabetic Retinopathy / drug therapy*
  • Erythropoietin / administration & dosage*
  • Erythropoietin / pharmacokinetics
  • In Situ Nick-End Labeling
  • Male
  • Microscopy, Electron
  • Polymerase Chain Reaction
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vitreous Body*


  • DNA Primers
  • Vascular Endothelial Growth Factor A
  • Erythropoietin