ADVANCED GLYCATION END-PRODUCTS INCREASE RETINAL VASCULAR ENDOTHELIALGROWTH-FACTOR EXPRESSION

Advanced glycation end products (AGEs) are linked with the development of diabetic retinopathy; however, the pathogenic mechanisms are poorl y defined. Vascular endothelial growth factor (VEGF) levels are increa sed in ischemic and nonischemic diabetic retina, and VEGF is required for the development of retinal and iris neovascularization. Moreover, VEGF alone can induce much of the concomitant pathology of diabetic re tinopathy. In this study, we found that AGEs increased VEGF mRNA level s in the ganglion, inner nuclear, and retinal pigment epithelial (RPE) cell layers of the rat retina. In vitro, AGEs increased VEGF mRNA and secreted protein in human RPE and bovine vascular smooth muscle cells , The AGE-induced increases in VEGF expression were dose-and time-depe ndent, inhibited by antioxidants, and additive with hypoxia, Use of an anti-VEGF antibody blocked the capillary endothelial cell proliferati on induced by the conditioned media of AGE-treated cells. AGEs may par ticipate in the pathogenesis of diabetic retinopathy through their abi lity to increase retinal VEGF gene expression.