Blockade of vascular adhesion protein-1 attenuates choroidal neovascularization

Nami Yoshikawa, Kousuke Noda, Yoko Ozawa, Kazuo Tsubota, Yukihiko Mashima, Susumu Ishida

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8 Citations (Scopus)

Abstract

Purpose: Vascular adhesion protein (VAP)-1 is an adhesion molecule elucidated as a mediator of the leukocyte recruitment cascade. The purpose of this study was to investigate the role of VAP-1 in ocular inflammatory neovascularization using a mouse laser-induced choroidal neovascularization (CNV) model. Methods: CNV was induced with 532 nm laser irradiation in C57BL/6 mice, and production of VAP-1 protein in the retinal pigment epithelium (RPE) choroid during CNV formation was examined. CNV animals were treated with the specific VAP-1 inhibitor U-V002 or vehicle solution, and the volume of CNV tissue was evaluated with volumetric measurements. Macrophage infiltration into the CNV lesions was evaluated using two different techniques, flatmount staining and real-time polymerase chain reaction (PCR) for F4/80. The protein levels of intercellular adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1, P-selectin, and vascular endothelial growth factor (VEGF) in the RPE-choroid were measured with enzyme-linked immunosorbent assay (ELISA). Results: VAP-1 inhibition significantly suppressed CNV formation in a dose-dependent manner and reduced macrophage infiltration into CNV lesions. Furthermore, VAP-1 blockade decreased the expression of ICAM-1 and MCP-1, both of which play a pivotal role in macrophage recruitment. Conclusions: Our data suggest VAP-1 has an important role during ocular inflammatory neovascularization through leukocyte recruitment. VAP-1 inhibition may be a novel and potent therapeutic strategy in treating CNV formation.

Original languageEnglish
Pages (from-to)593-600
Number of pages8
JournalMolecular vision
Volume18
Publication statusPublished - 2012 Mar 2

ASJC Scopus subject areas

  • Ophthalmology

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    Yoshikawa, N., Noda, K., Ozawa, Y., Tsubota, K., Mashima, Y., & Ishida, S. (2012). Blockade of vascular adhesion protein-1 attenuates choroidal neovascularization. Molecular vision, 18, 593-600.