RESEARCH ARTICLE


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
1 Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan
2 Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan
3 Department of Medical Biochemistry, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
4 Tulane University Health Sciences Center, Tulane University Hebert Center, Bldg. 30, US-Japan Biomedical Research Laboratories, Belle Chasse, USA

Article Information


Identifiers and Pagination:

Year: 2008
Volume: 2
First Page: 79
Last Page: 86
Publisher Id: TOPHARMJ-2-79
DOI: 10.2174/1874143600802010079

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

© 2008 Kobayashi et al.

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.

* Address correspondence to this author at the Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, 3-Ho Kanagawa-Machi, Kanazawa 920-1181, Japan; Tel: +81-76-229-1165; Fax: +81-76-229-2781; E-mail: s-kobayashi@hokuriku-u.ac.jp


Abstract

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.

Keywords: Proliferative diabetic retinopathy, retinal neovascularization, Nε-(carboxymethyl)lysine, choroidal neovasculari-zation, tumor necrosis factor α, vascular endothelial growth factor.