April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Endogenous Erythropoietin is Required to Preserve Retinal Function Following Oxygen-Induced Retinopathy in the Mouse
Author Affiliations & Notes
  • F. Mowat
    Department of Genetics, UCL Institute of Ophthalmology, London, United Kingdom
  • F. Gonzalez
    Department of Genetics, UCL Institute of Ophthalmology, London, United Kingdom
    Department of Physiology, School of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain
  • Y. Duran
    Department of Genetics, UCL Institute of Ophthalmology, London, United Kingdom
  • U. F. O. Luhmann
    Department of Genetics, UCL Institute of Ophthalmology, London, United Kingdom
  • A. J. Smith
    Department of Genetics, UCL Institute of Ophthalmology, London, United Kingdom
  • P. H. Maxwell
    Division of Medicine, University College London, London, United Kingdom
  • R. R. Ali
    Department of Genetics, UCL Institute of Ophthalmology, London, United Kingdom
    NIHR Biomedical Centre for Ophthalmology, London, United Kingdom
  • J. W. B. Bainbridge
    Department of Genetics, UCL Institute of Ophthalmology, London, United Kingdom
    NIHR Biomedical Centre for Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships  F. Mowat, None; F. Gonzalez, None; Y. Duran, None; U.F.O. Luhmann, None; A.J. Smith, None; P.H. Maxwell, None; R.R. Ali, None; J.W.B. Bainbridge, None.
  • Footnotes
    Support  Wellcome Trust Grant 074617/Z/04/Z
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4468. doi:
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      F. Mowat, F. Gonzalez, Y. Duran, U. F. O. Luhmann, A. J. Smith, P. H. Maxwell, R. R. Ali, J. W. B. Bainbridge; Endogenous Erythropoietin is Required to Preserve Retinal Function Following Oxygen-Induced Retinopathy in the Mouse. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4468.

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

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Abstract

Purpose: : Murine oxygen-induced retinopathy (OIR) is a reproducible model of ischemia-induced retinal neovascularization and has been used extensively to investigate the effects of novel anti-angiogenic treatments including inhibitors of VEGF and erythropoietin (Epo). The aim of this study was to evaluate the neurodegenerative effects of ischemia in murine OIR, and the importance of endogenous Epo in protecting the retina against degeneration and dysfunction.

Methods: : We evaluated retinal degeneration by TUNEL staining during early OIR, and by quantifying retinal thickness at p60 following OIR. We assessed retinal function by dark- and light-adapted electroretinography (ERG) at p26 and p60. We quantified Epo expression and retinal ischemia/neovascularisation following OIR, and investigated the effect of Epo deficiency on the vascular and neuronal responses using heterozygote EpoTAg mice. To determine if retinal dysfunction in Epo deficient mice was reversible, we administered recombinant human Epo (rHuEPO) systemically.

Results: : OIR was associated with retinal dysfunction, as indicated by significant suppression of dark-adapted ERG a- and b-wave amplitudes, oscillatory potentials and light-adapted flicker amplitudes, and also with significant structural degeneration of the inner retina. OIR was associated with a reduction in hematocrit, and upregulation of Epo expression in both the retina and kidney. Despite Epo deficiency, the retinal neovascular response to OIR and structural degeneration in EpoTAg mice was unchanged. Epo deficiency was associated, however, with more profound retinal dysfunction, as indicated by greater suppression of a- and b- wave amplitudes, which could be rescued transiently by systemic rHuEPO administration.

Discussion: : Murine OIR offers a valuable model of retinal ischemic neurodegeneration and dysfunction in which to investigate endogenous responses and to evaluate novel therapeutic approaches. Endogenous expression of Epo can have a neuroprotective role on retinal function that should be considered when designing anti-angiogenic therapies based on Epo inhibition.

Keywords: hypoxia • inner retina dysfunction: biochemistry and cell biology • neuroprotection 
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