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Neuroprotective role of erythropoietin by antiapoptosis in the retina

Authors

  • Hyewon Chung,

    1. Department of Ophthalmology, Asan Medical Center, Seoul, Korea
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  • Hyunju Lee,

    1. Department of Ophthalmology, University of South Carolina, Columbia, South Carolina
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  • Folami Lamoke,

    1. Department of Ophthalmology, University of South Carolina, Columbia, South Carolina
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  • William J. M. Hrushesky,

    1. Medical Chronobiology Laboratory, Dorn Research Institute, William Jennings Bryan Dorn Veterans Affairs Medical Center, School of Medicine, and School of Public Health, University of South Carolina, Columbia, South Carolina
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  • Patricia A. Wood,

    1. Medical Chronobiology Laboratory, Dorn Research Institute, William Jennings Bryan Dorn Veterans Affairs Medical Center, School of Medicine, and School of Public Health, University of South Carolina, Columbia, South Carolina
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  • Wan Jin Jahng

    Corresponding author
    1. Department of Ophthalmology, University of South Carolina, Columbia, South Carolina
    2. Vision Research Laboratory, Julia Eye Institute, Hopkins, South Carolina
    • Department of Ophthalmology, University of South Carolina, Columbia, SC 29203
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Abstract

Erythropoietin (EPO) stimulates red blood cell production, in part by inhibiting apoptosis of the red blood cell precursors. The erythropoietic effects of EPO are circadian stage dependent. Retinal injury due to light occurs through oxidative mechanisms and is manifest by retinal and retinal pigment epithelium (RPE) cells apoptosis. The visual cycle might be circadian coordinated as a means of effectively protecting the retina from the detrimental effects of light-induced, oxygen-dependent, free radical–mediated damage, especially at the times of day when light is more intense. We show that the retinal expression of EPO and its receptor (EPOR), as well as subsequent Janus kinase 2 (Jak2) phosphorylations, are each tightly linked to a specific time after oxidative stress and in anticipation of daily light onset. This is consistent with physiological protection against daily light-induced, oxidatively mediated retinal apoptosis. In vitro, we verify that EPO protects RPE cells from light, hyperoxia, and hydrogen peroxide–induced retinal cell apoptosis, and that these stimuli increase EPO and EPOR expression in cultured RPE cells. Together, these data support the premise that EPO and its EPOR interactions represent an important retinal shield from physiologic and pathologic light-induced oxidative injury. © 2009 Wiley-Liss, Inc.

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