Vascular adhesion protein-1 blockade suppresses choroidal neovascularization.| Authors: | Kousuke Noda, Haicheng She, Toru Nakazawa, Toshio Hisatomi, Shintaro Nakao, Lama Almulki, Souska Zandi, Shinsuke Miyahara, Yasuhiro Ito, Kennard L Thomas, Rebecca C Garland, Joan W Miller, Evangelos S Gragoudas, Yukihiko Mashima, Ali Hafezi-Moghadam | | Language: | ENG. | | Date: | 7-5-2008 | | Journal: | The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(1530-6860)
| | Release: | FASEB J. 6 May 2008 | |
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Abstract:
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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) -alpha, 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.
| | Copyright: | The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
*Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA;Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; andR-tech Ueno, Ltd., Tokyo, Japan. | | Full text: | | | |
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