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Cellular and Molecular Neurobiology

, Volume 28, Issue 2, pp 317–329 | Cite as

Up-regulated Endogenous Erythropoietin/Erythropoietin Receptor System and Exogenous Erythropoietin Rescue Retinal Ganglion Cells after Chronic Ocular Hypertension

  • Qing-Ling Fu
  • Wutian Wu
  • Hua Wang
  • Xin Li
  • Vincent W. H. Lee
  • Kwok-Fai SoEmail author
Original Paper

Abstract

Aims

Recent studies have showed that erythropoietin (EPO) is a neuroprotectant for central nerve system neurons in addition to being a hematopoietic cytokine in response to hypoxia. In this study, we investigate the role of the EPO/EPO receptor (EPOR) system in the rat retina after ocular hypertension injury that mimics glaucoma.

Methods

Elevated intraocular pressure was induced by laser coagulation of the episcleral and limbal veins. Expression of EPO and EPOR in the normal and glaucomous retinas was investigated by immunohistochemistry and Western blot. To examine the effects of endogenous EPO on the survival of retinal ganglion cells (RGCs) subjected to hypertensive injury, soluble EPOR was directly injected into the vitreous body. Recombinant human EPO was both intravitreally and systemically administrated to study the effect of exogenous EPO on the survival of RGCs after ocular hypertension injury.

Results

Immunohistochemistry studies identified Müller cells as the main source of EPO in the normal retina. Expression of EPO and EPOR proteins was increased significantly 2 weeks after ocular hypertension. RGCs, amacrine and bipolar cells all demonstrated an increased expression of EPOR after ocular hypertension. Neutralization of endogenous EPO with soluble EPOR exacerbated ocular hypertensive injury, suggesting a role of the EPO/EPOR system in the survival of RGCs after injury. Similarly, topical and systemic administration of recombinant human EPO rescues RGCs after chronic ocular hypertension.

Conclusions

These results indicate that an endogenous EPO/EPOR system participates in intrinsic recovery mechanisms after retina injury and RGCs might be rescued by exogenous administration of EPO.

Keywords

Erythropoietin Erythropoietin receptor Retinal ganglion cell Glaucoma Intraocular pressure Endogenous Neuroprotectant 

Notes

Acknowledgement

We gratefully acknowledge Dr. Daniel HS Lee from Biogen Idec, Inc. USA for his valuable comments. This research is supported by a donation from the Hong Kong Eye Charitable Foundation, and Ms. Annie Tso Wen Wei.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Qing-Ling Fu
    • 1
    • 2
  • Wutian Wu
    • 1
    • 2
  • Hua Wang
    • 1
    • 2
  • Xin Li
    • 1
    • 2
  • Vincent W. H. Lee
    • 3
  • Kwok-Fai So
    • 1
    • 2
    Email author
  1. 1.Department of AnatomyThe University of Hong Kong Li Ka Shing Faculty of MedicinePokfulamHong Kong SAR, China
  2. 2.The State Key Laboratory of Brain and Cognitive sciencesThe University of Hong KongPokfulamHong Kong SAR, China
  3. 3.Eye CentreHong Kong Adventist HospitalHong KongHong Kong SAR, China

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