Biol. Pharm. Bull. 30(1) 133—138 (2007)

through the formation of early products such as Schiff base and Amadori rearrangement products, to the formation of advanced glycation endproducts (AGEs). Ne-(Carboxymethyl)lysine (CML), a major structure in AGEs, is accumulated in several tissues of human and animal during aging and various disease states including age-related macular degeneration (AMD). Choroidal neovascularization leads the cause of rapid severe vision loss in patients with AMD. Vascular endothelial growth factor (VEGF) could be implicated in the development of choroidal neovascularization found in the disease of AMD. In the animal models of AMD, choroidal neovascularization is induced by sub retinal injection of vectors encoding growth factors such as VEGF. We have developed an in vitro culture system to study the condition of choroidal capillaries, and showed the evidence that CML adduct facilitates proliferation of CD34 endothelial progenitor cells in immature choroidal microvessels. The CML adduct releases VEGF, tumor necrosis factor (TNF) a and platelet-derived growth factor (PDGF)-B, and facilitate neovascularization in choroidal capillary explants of normal young and early stage of streptozotocin (STZ)-diabetic rats. The advanced stage of STZ-diabetic rats increased the neovascularization greater than the early stage did. In the present study, we investigated the neovascularization in cultured choroidal explants of aged rats to clarify actions of CML adduct on the growth of sprouting and buds of choroidal capillaries (neovascularization) in culture. Roles of CML adduct for the release of angiogenic factors including VEGF, TNF a and PDGF-B from cultured choroidal capillary were also examined in the aged rat.