April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Anti-VEGF Effects of Intravitreal Erythropoietin in Early Diabetic Retinopathy
Author Affiliations & Notes
  • J. Zhang
    Tongji Eye Institute and Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, China
    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
  • L.-M. Hu
    Dept. of Ophthalmology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
  • G. Xu
    Dept. of Ophthalmology, Second Affiliated Hospital of Soochow University, Suzhou, China
  • Y. Wu
    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
  • J. Shen
    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
  • Y. Luo
    Dept. of Ophthalmology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
  • Y. Zhong
    Dept. of Ophthalmology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
  • S. H. Sinclair
    Dept. of Ophthalmology, Drexel University College of Medicine, Philadelphia, Pennsylvania
  • W. Li
    Dept. of Ophthalmology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
    Dept. of Ophthalmology, Drexel University College of Medicine, Philadelphia, Pennsylvania
  • G.-T. Xu
    Tongji Eye Institute and Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, China
    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
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5601. doi:
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    • Get Citation

      J. Zhang, L.-M. Hu, G. Xu, Y. Wu, J. Shen, Y. Luo, Y. Zhong, S. H. Sinclair, W. Li, G.-T. Xu; Anti-VEGF Effects of Intravitreal Erythropoietin in Early Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5601.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To investigate the underlying mechanisms of the therapeutic effects of intravitreal erythropoietin (EPO) for early diabetic retinopathy (DR).

Methods: : A single intravitreal injection of EPO (8-160 mU/eye) was given to streptozotocin-induced diabetic rats at different time points during the course of diabetes. Blood-retinal barrier (BRB) permeability, neuronal apoptosis and retinal morphology were studied. In parallel, the key factors of hypoxia-inducible factor 1 alpha (HIF-1 alpha) pathway have been quantitatively studied, including VEGF-A, endogenous EPO, EPO receptor (EpoR), prolyl hydroxylases (PHD1-3) and von Hippel-Lindau tumor suppressor (VHL).

Results: : In the present study, a single intravitreal erythropoietin (EPO) to diabetic rats produced therapeutic effects on maintaining blood-retinal barrier (BRB) function and neuronal survival at different time courses of retinopathy. The mRNA levels of HIF-1 alpha, VEGF-A, endogenous EPO, PHD1-3 and VHL were 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 were also down-regulated by exogenous EPO.

Conclusions: : 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 exerts neuronal protection.

Keywords: diabetic retinopathy • apoptosis/cell death • retina 
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