N -(Carboxymethyl)Lysine-Induced Choroidal Angiogenic Potential Facili- tates 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 explant was co-cultured with advanced-diabetic choroidal explant, the number of retinal microvessels was significantly increased. Anti-CML antibody blocked the retinal changes caused by co-culture with both early-diabetic and advanceddiabetic choroidal explant. Antibodies against TNF and VEGF reduced the number of retinal microvessels in the coculture with advanced-diabetic choroidal explant. These results indicate that the CML-induced choroidal activity is associated 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.