Roles of N~(epsilon)-(carboxymethyl)lysine for neovascularization of cultured retinal capillary in early and advanced stages of streptozotocin-diabetic rats

摘要

Actions of the N~(epsilon)-(carboxymethyl)lysine (CML) were investigated on the neovascularization of cultured retinal explants in streptozotocin (STZ)-diabetic rats at the early and the advanced stages. The onset and growth of sprouting and buds inthe retinal explant (retinal neovascularization) in the early diabetes were similar to those in the age-matched young control. However, the retinal neovascularization in the advanced diabetes was significantly augmented, compared with those in the earlydiabetes and the age-matched aged control. Anti-CML antibody (6D12) did not affect the retinal neovascularization in the advanced diabetes. The retinal neovascularization was suppressed by the co-cultured choroidal explant in the early diabetes and facilitated by the choroidal explant in the advanced diabetic and the aged control, respectively. Anti-CML antibody inhibited this retinal neovascularization induced by the co-cultured choroidal explants. Anti-vascular endothelial growth factor (anti-VEGF) antibody also had a similar action as anti-CML antibody in the advanced diabetes. In conclusion, the CML-induced choroidal activity suppressed the retinal neovascularization in the early diabetes. During progression of diabetes, the retinal neovascularization was facilitated in a CML-independent manner. The CML-induced choroidal activity augmented the retinal neovascularization in the advanced diabetes. Both the CML-independent and CML-activated retinal neovascularization in the advanced diabetes may have a pathological role for the induction of proliferative diabetic retinopathy.