Vascular adhesion protein-1 blockade suppresses choroidal neovascularization

• Published in: The FASEB journal 2008-08, Vol.22 (8), p.2928-2935
• Main Authors: Noda, Kousuke, She, Haicheng, Nakazawa, Toru, Hisatomi, Toshio, Nakao, Shintaro, Almulki, Lama, Zandi, Souska, Miyahara, Shinsuke, Ito, Yasuhiro, Thomas, Kennard L, Garland, Rebecca C, Miller, Joan W, Gragoudas, Evangelos S, Mashima, Yukihiko, Hafezi-Moghadam, Ali
• Format: Article
• Language: English
• Subjects: age-related macular degeneration; Amine Oxidase (Copper-Containing) - antagonists & inhibitors; Amine Oxidase (Copper-Containing) - genetics; Amine Oxidase (Copper-Containing) - physiology; angiogenesis; Animals; Base Sequence; Cell Adhesion Molecules - antagonists & inhibitors; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - physiology; Cell Movement; Choroidal Neovascularization - etiology; Choroidal Neovascularization - pathology; Choroidal Neovascularization - physiopathology; Choroidal Neovascularization - prevention & control; DNA Primers - genetics; Gene Expression; Humans; Inflammation Mediators - metabolism; leukocyte recruitment; macrophage; Macrophages - pathology; Macrophages - physiology; Macular Degeneration - etiology; Rats; Rats, Inbred BN; Rats, Inbred Lew; Research Communications; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.07-105346

Vascular adhesion protein-1 (VAP-1) is an endothelial cell adhesion molecule involved in leukocyte recruitment. Leukocytes and, in particular, macrophages play an important role in the development of choroidal neovascularization (CNV), an integral component of age-related macular degeneration (AMD). Previously, we showed a role for VAP-1 in ocular inflammation. Here, we investigate the expression of VAP-1 in the choroid and its role in CNV development. VAP-1 was expressed in the choroid, exclusively in the vessels, and colocalized in the vessels of the CNV lesions. VAP-1 blockade with a novel and specific inhibitor significantly decreased CNV size, fluorescent angiographic leakage, and the accumulation of macrophages in the CNV lesions. Furthermore, VAP-1 blockade significantly reduced the expression of inflammation-associated molecules such as tumor necrosis factor (TNF) -α, monocyte chemoattractant protein (MCP) -1, and intercellular adhesion molecule (ICAM) -1. This work provides evidence for an important role of VAP-1 in the recruitment of macrophages to CNV lesions, establishing a novel link between VAP-1 and angiogenesis. Inhibition of VAP-1 may become a new therapeutic strategy in the treatment of AMD.--Noda, K., She, H., Nakazawa, T., Hisatomi, T., Nakao, S., Almulki, L., Zandi, S., Miyahara, S., Ito, Y., Thomas, K. L., Garland, R. C., Miller, J. W., Gragoudas, E. S., Mashima, Y., Hafezi-Moghadam, A. Vascular adhesion protein-1 blockade suppresses choroidal neovascularization.