Advanced Glycation End Products Affect Expression Of VEGF And Flk-1 In Retina

PurposeDiabetic retinopathy(DR)presents major therapeutic problems for the ophthalmologist and despite many decades of intense research it still constitutes a major cause of blindness.Advanced glycation end products(AGEs)are linked with the development of diabetic retinopathy,however,the pathogenic mechanisms are poorly defined.Vascular endothelial growth factor(VEGF)family and its receptor system has been shown to be the fundamental regulator in the cell signaling of angiogenesis. VEGF levels are increased in ischemic and nonischemic diabetic retina,and VEGF is required for the development of retinal neovascularization.Moreover,VEGF can induce much of the concomitant pathology of diabetic retinopathy.To investigate the mechanism of diabetic retinopathy,we examined whether AGEs could up-regulate expression of VEGF and flk-1 in rat retina.MethodPreparation of AGEs.BSA was glycated by incubation with D-glucose in PBS 37℃for 3 months.Dialyzed glycated protein was characterized based on fluorescence at 440 nm upon excitation at 360 nm using a fluorescence spectrometer.Control, nonglycated albumin consisted of the same initial preparations of albumin incubated in the same manner,except that no sugar was present.Intravenous injections of AGEs.20 SD rats were divided into AGEs group and BSA group at random.The rats were recieved injection of 40mg/kg.d AGEs and BSA respectively for 2 weeks.Immunohistochemistry.The rats were killed with Chloral Hydrate.In this study, the effect of AGEs induced VEGF and flk-1 expression was investigated using immunohistochemical method.ResultsBoth VEGF expression and flk-1 expression in AGEs group were much higher than in BSA group.ConclusionAGEs induced an increase in expression of VEGF and flk-1 in rat retina.Our results demonstrate that AGEs play a important role in diabetic retinopathy.