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K. Bigot, E. Perez, S. Gadin, O. Roche, M. Menasche, M. Abitbol; Effect of systemic erythropoietin treatment on photoreceptors degeneration of RCS rats. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3583.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Erythropoietin (Epo) is recognized for its central role in differentiation and proliferation of erythroid precursor cells. Nevertheless, recent studies reported that Epo also mediates neuroprotection by binding to its transmembrane receptor (EpoR) expressed in brain. The purpose of the present study was to evaluate the potential neuroprotective effect of erythropoietin treatment on the RCS retinal degeneration. Methods: From 1 to 18 days of age, two groups of RCS rats were submitted to a daily intraperitoneal injection of rhEPO (5000 IU/kg; Epo group) or saline solution (SP group), respectively. Following analyzes were performed on 21–, 28–, 35– and 45–day–old animals. retinal function was assessed by electroretinography (ERG). Expression of EpoR gene in retina was examined by RT–PCR and the localizations of Epo and EpoR proteins in the eye were determinated by immunohistochemistry. Results: In 21– and 28–day–old animals, no ERG difference was observed for rod activity, whatever the treatment used. At 35 days of age, the amplitude of the rod b–wave was significantly higher in Epo group compared to SP group (P=0.0428). This increased amplitude displayed a tendency to persist at least until 45 days of age. Similarly to what has been reported in the brain, we showed by RT–PCR the presence of EpoR splice variants in retinal cells. Epo and EpoR proteins were both expressed in lens, corneal epithelium, inner segments of photoreceptors, inner nuclear layer and in ganglion cell layer. Localization of Epo in plexiform layers remains to be confirmed. Conclusions:This study demonstrates that rat retinal cells express Epo and its receptor. The processing of the EpoR pre–messenger transcripts seems likely to be specific in the retina. According to our preliminary results, systemic administration of Epo to RCS rats appears to exert in vivo a neuroprotective effect on photoreceptors. Detailed histological analysis is still being completed. The underlying mechanisms of this neuroprotective effect prompted us to launch a large scale pre–clinical study.
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