Expression And Mechanism Of EPO And EPOR In Diabetic Retinopathy

Erythropoietin(EPO) has been viewed traditionallyas a hematopoietic cytokine produced by fetal liver and adult kidney in response to hypoxia .Lately,more evidence suggests that EPO has other functions.Epo and EpoR are expressed in the human retina and central nervous system.Retina is the most metabolically acive tissue in the human body and, therefore,is highly sensitive to reductions in oxygen tension.Hypoxia-inducible factor(HIF)is the primary hypoxic signaling protein in cells for regulating angiogeniesis and is able to induce the transcription of more than 70 genes,such as Epo and VEGF.Apart from the described oxygen-dependent regulation of HIF-1αsubunits,in recent years,there is a potially unifying pathway for oxygen-indepdent HIFαactivation has been identified:the mam- malian target of rapamycin(mTOR).Many studies show that the use of mTOR inhibitors leads to attenuation of HIF activation and decrease the expressi-on of VEGF.They postulated that HIF becomes more stable by heightened mTOR activity or,mTOR enhances the transcriptional activity of HIF-1α.Since mTOR can stimulate the expression of VEGF through HIF-1α,it may also stimulate the expression of Epo.In present study,we found a higher expression of Epo,EpoR,VEGF,HIF-1αand mTOR in the retina of diabetic retinaopathy.We pros-tulated that elevated Epo and VEGF expression in diabetic retina may due to the HIF-1αstimulated by mTOR .Diabetic retinopathy(DR) is the leading cause of blindness in patients 20 to 70 years.It has become increasingly clear that DR affects not only retinal vasculature,but also retinal neuronal and glial cells.Our stuty found that the elevated expression of GFAP and decrease retinal ganglion cells in DR.Support the injury of retina neural cells in DR.In human eyes with DR and PDR,elevated Epo levels were detected in the retina and vitreous,suggesting that Epo is related to the proceture of DR.Epo is a neuroprotectant factor in DR,it is also related to the neovascularization of PDR.