1. Blockade of vascular adhesion protein-1 attenuates choroidal neovascularization
- Author
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Yoshikawa, Nami, Noda, Kousuke, Ozawa, Yoko, Tsubota, Kazuo, Mashima, Yukihiko, and Ishida, Susumu
- Subjects
Choroidal Neovascularization/metabolism ,Enzyme Inhibitors/administration & dosage ,Signal Transduction/drug effects ,Enzyme Inhibitors/therapeutic use ,Male ,Intercellular Adhesion Molecule-1/genetics ,Retinal Pigment Epithelium/metabolism ,Retinal Pigment Epithelium/blood supply ,Vascular Endothelial Growth Factor A/metabolism ,Chemokine CCL2/genetics ,Intercellular Adhesion Molecule-1/metabolism ,Cell Movement/drug effects ,P-Selectin/genetics ,Choroid/metabolism ,Vascular Endothelial Growth Factor A/genetics ,Mice ,Macrophages/drug effects ,Cell Adhesion Molecules/metabolism ,Lasers ,Amine Oxidase (Copper-Containing)/metabolism ,Mice, Inbred C57BL ,P-Selectin/metabolism ,Dose-Response Relationship, Drug ,Choroidal Neovascularization/drug therapy ,Amine Oxidase (Copper-Containing)/antagonists & inhibitors ,Retinal Pigment Epithelium/drug effects ,Thiazoles/administration & dosage ,Choroid/blood supply ,Cell Adhesion Molecules/antagonists & inhibitors ,Choroid/drug effects ,Gene Expression ,Animals ,Thiazoles/therapeutic use ,Chemokine CCL2/metabolism - 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.
- Published
- 2012