April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Anti-VEGF Effects Through Negative Feedback Regulation With Intravitreal Injection of Erythropoietin in Early Diabetic Retinopathy
Author Affiliations & Notes
  • G.-T. Xu
    Laboratory of Clinical Visual Sciences, 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, Shanghai, China
  • J. Zhang
    Laboratory of Clinical Visual Sciences, 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, Shanghai, China
  • L.-M. Hu
    Dept. of Ophthalmology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
  • W. Li
    Laboratory of Clinical Visual Sciences, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    Dept. of Ophthalmology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
  • W. Li
    Dept. of Ophthalmology, Drexel University College of Medicine, Philadelphia, Pennsylvania
  • Footnotes
    Commercial Relationships  G.-T. Xu, None; J. Zhang, None; L.-M. Hu, None; W. Li, None; W. Li, None.
  • Footnotes
    Support  (1) China National Program on Key Basic Research Project (973), 2004CB720300; (2) Unrestricted Research Fund from the Clear Vision Foundation, Philadelphia USA.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 36. doi:
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    • Get Citation

      G.-T. Xu, J. Zhang, L.-M. Hu, W. Li, W. Li; Anti-VEGF Effects Through Negative Feedback Regulation With Intravitreal Injection of Erythropoietin in Early Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):36.

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

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Abstract

Purpose: : Since intravitreal erythropoietin (EPO) is able to restore blood-retinal barrier of diabetic rats (Invest Ophthalmol Vis Sci 2008;49:732-742), the inhibitory mechanism of EPO on VEGF is explored.

Methods: : A single intravitreal injection of EPO was given to streptozotocin-induced diabetic rats at 2, 4 weeks and 5 months after diabetes onset. BRB permeability was studied, along with the detection of hypoxia-inducible factor 1 (HIF-1) pathway, including vascular endothelial growth factor A (VEGF-A), endogenous EPO, EPO receptor (EpoR), prolyl hydroxylases (PHD1-3) and von Hippel-Lindau tumor suppressor (VHL) by real-time PCR and Western blot.

Results: : EPO administered after diabetic onset effectively maintained BRB function. The mRNA levels of HIF-1, 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, VEGF-A, and endogenous EPO in diabetic retinas were also significantly down-regulated by exogenous EPO. A generalized decrease in VEGF distribution throughout the EPO-treated diabetic retina was demonstrated by immunofluorescence.

Conclusions: : Activation of the HIF-1 pathway was observed in early diabetic retina. The regulation of HIF-1 pathway by exogenous EPO was documented at both transcriptional and translational levels. This down-regulation of HIF-1 pathway was presumably achieved by a negative feedback mechanism at therapeutic levels of EPO. EPO appears to lead to suppression of VEGF and in turn, restoration of the normal functions of BRB.

Keywords: diabetic retinopathy • protective mechanisms • vascular endothelial growth factor 
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