Previous studies have shown that systemic up-regulation of erythropoietin (Epo) protects retina from light-induced retinal degeneration. Aranesp (darbepoetin alfa) and AMG114, hyperglycosylated forms of Epo, are recently developed Epo-analogs with an extended circulating half-life in vivo. We tested the protective effect of intravitreal injection of Epo glycosylation analogs in a rat model of retinal degeneration. Albino rats were injected in one eye with 0.2, 2, 20 ng of Aranesp or AMG114, and in the other eye with carrier, and then exposed to bright light (2,700 lx for 6 h) 2 days after the injection. Seven days after the light exposure, electroretinograms (ERG) were recorded and eyes were removed to measure outer nuclear layer (ONL) thickness. The retinal protection due to local injury and systemic anesthesia related to the intravitreal injection procedure was observed at day 1, but was significantly decreased by day 2. The ERG b-wave amplitudes and ONL thickness were not significantly different between right and left eyes in any of experimental groups, indicating no retinal protection by the Epo-analogs functionally and structurally. Aranesp and AM114 delivered intravitreally do not protect rod photoreceptor cells from light-induced damage.
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The authors are grateful to Mark Dittmar (Dean A. McGee Eye Institute) for maintaining the animals used in this study and to Louisa J. Williams and Linda S. Boone (Dean A. McGee Eye Institute) for their excellent retinal section preparation. This study was supported by a contract from Amgen, Inc. (Thousand Oaks, CA) and grants from the National Eye Institute (EY04149, EY00871, and EY12190); National Center for Research Resources (RR17703); Research to Prevent Blindness, Inc.; and the Foundation Fighting Blindness.
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