Nε-(Carboxymethyl)Lysine-Induced Choroidal Angiogenic Potential Facilitates Retinal Neovascularization in Advanced-Diabetic Rat In Vitro

N  -(Carboxymethyl)lysine (CML) over-stimulates choroidal neovascularization in vitro in streptozotocin (STZ)-diabetic rat. In this study, we investigated the effects of CML-induced choroidal angiogenic potential on retinal neovascularization during the course of STZ-induced diabetes in rats. Retinal and choroidal explants were isolated from the same eyeball of early-diabetic, advanced-diabetic and age-matched normal rats. When retinal explant was co-cultured with early-diabetic choroidal explant, the number of retinal microvessels was significantly decreased. When retinal ex- plant was co-cultured with advanced-diabetic choroidal explant, the number of retinal microvessels was significantly in- creased. Anti-CML antibody blocked the retinal changes caused by co-culture with both early-diabetic and advanced- diabetic choroidal explant. Antibodies against TNF  and VEGF reduced the number of retinal microvessels in the co- culture with advanced-diabetic choroidal explant. These results indicate that the CML-induced choroidal activity is asso- ciated with the angiogenic actions of TNF  and VEGF on retinal capillaries in advanced diabetes. During the course of diabetic retinopathy, different actions on retinal neovascularization may operate.