학술논문

Vascular adhesion protein-1 blockade suppresses choroidal neovascularization.
Document Type
Article
Source
FASEB Journal. Aug2008, Vol. 22 Issue 8, p2928-2935. 8p. 6 Diagrams, 3 Graphs.
Subject
*CELL adhesion molecules
*NEOVASCULARIZATION
*RETINAL degeneration
*LEUCOCYTES
*MACROPHAGES
Language
ISSN
0892-6638
Abstract
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. [ABSTRACT FROM AUTHOR]