A Study On The Protective Function Of Erythropoietin To The Rat Retina After Acute Intraocular Hypertension

Purpose: To investigate the protective function and mechanism of recombinant human erythropoietin (rhEPO) pretreatment on the rat retina with acute intraocular hypertension injury.Methods:36 healthy Wistar rats (♂) were randomly divided into 3 groups: normal group(n=4, killed directly without any treatment), saline group(n=16, physiological saline was administered ip. 3 hours before raising intraocular pressure), rhEPO group(n=16, rhEPO was administered ip. 3 hours before raising intraocular pressure). Either of bilateral eyes was randomly made into the acute high intraocular pressure(IOP) model using the method of saline perfusion into anterior chamber until the IOP reached 100mmHg, then sustained the IOP for 60 minutes. All the rats were killed respectively and the eyeballs were enucleated at different observation periods after the model was successfully established(6h, 24h, 48h, 72h). The histological changes of retina were observed by HE staining; the expression and distribution of apoptotic cells and p-Akt protein were observed respectively by using TUNEL detection and immunohistochemistry. The data was statistically analyzed.Results:①The acute high intraocular pressure damaged the rat retina, the inner layer of retina got thinner and its percentage of whole retina was decreasing in the saline group, but the percentage of the rhEPO group was bigger than that of the saline group, the difference was significant(p<0.01);②No TUNEL-positive cells were seen in the normal group, the apoptotic cells of the other two groups were observed in the retinal ganglion cell layer(GCL) and inner nuclear layer(INL). There were less apoptotic cells in the rhEPO group than those in the saline group, the difference was significant (p<0. 01) ;③The minute expression of p-Akt protein was found in the normal group, while the p-Akt positive cells which were expressed in the RGL, inner plexiform layer(IPL) and INL were observed both in the saline group and the rhEPO group. There were stronger expression in the rhEPO group than those in the saline group, the difference was of significance(p<0.01). The expression of p-Akt in RGL and INL is stronger than that in IPL.Conclusion: The damage which caused by the acute intraocular hypertension was mainly occurred in RGL, IPL and INL, while rhEPO pretreatment can lessen the damage and the cell apoptosis. The mechanism of rhEPO's protective function may be the activation of PI3K/Akt signaling pathway and up regulation p-Akt in retina, which can restrain cell apoptosis.