Nε-(Carboxymethyl)Lysine-Induced Choroidal Angiogenic Potential Facilitates Retinal Neovascularization in Advanced-Diabetic Rat In Vitro
Shinjiro Kobayashi*, 1, 2, Masaaki Nomura1, Tatsuo Takahashi1, Miho Suzuki1, Ryoji Nagai 3, Nobuyoshi Hagino 4
Identifiers and Pagination:Year: 2008
First Page: 79
Last Page: 86
Publisher Id: TOPHARMJ-2-79
Article History:Received Date: 12/6/2008
Revision Received Date: 9/7/2008
Acceptance Date: 14/07/2008
Electronic publication date: 8/8/2008
Collection year: 2008
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Nε-(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 α 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 α and VEGF on retinal capillaries in advanced diabetes. During the course of diabetic retinopathy, different actions on retinal neovascularization may operate.