Therapeutic Effects Of EsRAGE Gene Modified OECs Transplantation On Diabetic Retinopathy

Background and purpose：Diabetic retinopathy (DR) has been one of the four primary reasons causingblind, which is the main one of the diabetic complications. The treatments includedrug,laser therapy and anti-VEGF therapy, which can’t cure the disease, but suppressthe development of it, so it has been an international problem. Capillaries repairingcould be a pivotal therapy, for DR is a kind of disease with the microvascular injured.In recent years, outgrowth endothelial cells (OECs) become a hot spot for its functionof repairing microvascular. In addition, advanced glucation end products and itsreceptor (AGEs-RAGE) play an important role in the pathogenesis of diabeticcomplications including retinopathy, cardiomyopathy and nephropathy. Andendogenous secretory RAGE is a splice variants of RAGE, which can decoy AGEsand block the inflammatory response.The purpose of this study is to explore whether esRAGE gene modified OECs(esRAGE-OECs) transplantation in diabetic retinopathy can be a novel cell therapyfor diabetic retinopathy. we observe the effect of the cells on rat retina and investigateVEGF and TGF-β expression of retina.Methods：50male SD rats were divided into4groups randomly,8for the control groupand the others for diabetic group. Diabetic rats were induced by intraperitonealinjection with1%streptozotocin (STZ) and the control were managed with citratebuffer solution. OECs and esRAGE gene modified OECs (esRAGE-OECs) weredelivered intravitreal injection in animals after more than3months.4weeks later,fluorescein fundus angiography was used to observed fluorescence duration for eachgroup and6months diabetic rats. And eyeballs were enucleared for making retinalparaffin sections which were used to observed the morphological changes andexpressing of VEGF and TGF-β after transplantation of aimed cells. Result：（1） The data shows that6-month diabetic rats had more severe DR than3-month in retinal angiography.（2）Pathological examination showed an appearanceof edema in every layer, hyperemia in ganglion cell layer’ capillary vessel, cellnumbers decreased in retinal nerve fiber layer and disordered arrangemet in inner andouter nuclear layer of retina in diabetes group, but milder pathological changes inesRAGE-OECs group.（3）In immunohistochemical staining, compared with CONgroup, expression of retinal VEGF and TGF-β shows increased in the DR,OECs,esRAGE-OECs group (P＜0.05). esRAGE-OECs group’s VEGF and TGF-βexpression show weaker level than DR and OECs group(P＜0.05).Conclusions：Our results suggest that intravitreal injection of esRAGE-OECs may be a noveltherapies for diabetic retinopathy by inhibiting VEGF, TGF-β expression andhemodynamic improvement.