Vascular adhesion protein-1 blockade suppresses choroidal neovascularization

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

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2928-2935
Number of pages8
JournalFASEB Journal
Volume22
Issue number8
DOIs
Publication statusPublished - 2008 Aug

Keywords

  • Age-related macular degeneration
  • Angiogenesis
  • Leukocyte recruitment
  • Macrophage

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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