Blockade of vascular adhesion protein-1 attenuates choroidal neovascularization.
Copyright policy )Blockade of vascular adhesion protein-1 attenuates choroidal neovascularization.
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.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).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.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.
- Keio University Japan
- Hokkaido University Japan
- Hokkaido Bunkyo University Japan
Male, Amine Oxidase (Copper-Containing)/metabolism, Choroid/metabolism, Gene Expression, Cell Movement/drug effects, Retinal Pigment Epithelium, Inbred C57BL, Choroid/blood supply, P-Selectin/genetics, Mice, Macrophages/drug effects, Thiazoles/administration & dosage, Cell Movement, Signal Transduction/drug effects, Enzyme Inhibitors, Chemokine CCL2, Chemokine CCL2/genetics, Enzyme Inhibitors/therapeutic use, Vascular Endothelial Growth Factor A/metabolism, Intercellular Adhesion Molecule-1/metabolism, Intercellular Adhesion Molecule-1, P-Selectin, P-Selectin/metabolism, Enzyme Inhibitors/administration & dosage, Choroid/drug effects, Amine Oxidase (Copper-Containing), Drug, Cell Adhesion Molecules/metabolism, Signal Transduction, Choroidal Neovascularization/metabolism, 496, Cell Adhesion Molecules/antagonists & inhibitors, Dose-Response Relationship, Vascular Endothelial Growth Factor A/genetics, Animals, Intercellular Adhesion Molecule-1/genetics, Retinal Pigment Epithelium/blood supply, Retinal Pigment Epithelium/metabolism, Dose-Response Relationship, Drug, Choroid, Lasers, Macrophages, Choroidal Neovascularization/drug therapy, Retinal Pigment Epithelium/drug effects, Choroidal Neovascularization, Mice, Inbred C57BL, Thiazoles, Amine Oxidase (Copper-Containing)/antagonists & inhibitors, Chemokine CCL2/metabolism, Thiazoles/therapeutic use, Cell Adhesion Molecules
Male, Amine Oxidase (Copper-Containing)/metabolism, Choroid/metabolism, Gene Expression, Cell Movement/drug effects, Retinal Pigment Epithelium, Inbred C57BL, Choroid/blood supply, P-Selectin/genetics, Mice, Macrophages/drug effects, Thiazoles/administration & dosage, Cell Movement, Signal Transduction/drug effects, Enzyme Inhibitors, Chemokine CCL2, Chemokine CCL2/genetics, Enzyme Inhibitors/therapeutic use, Vascular Endothelial Growth Factor A/metabolism, Intercellular Adhesion Molecule-1/metabolism, Intercellular Adhesion Molecule-1, P-Selectin, P-Selectin/metabolism, Enzyme Inhibitors/administration & dosage, Choroid/drug effects, Amine Oxidase (Copper-Containing), Drug, Cell Adhesion Molecules/metabolism, Signal Transduction, Choroidal Neovascularization/metabolism, 496, Cell Adhesion Molecules/antagonists & inhibitors, Dose-Response Relationship, Vascular Endothelial Growth Factor A/genetics, Animals, Intercellular Adhesion Molecule-1/genetics, Retinal Pigment Epithelium/blood supply, Retinal Pigment Epithelium/metabolism, Dose-Response Relationship, Drug, Choroid, Lasers, Macrophages, Choroidal Neovascularization/drug therapy, Retinal Pigment Epithelium/drug effects, Choroidal Neovascularization, Mice, Inbred C57BL, Thiazoles, Amine Oxidase (Copper-Containing)/antagonists & inhibitors, Chemokine CCL2/metabolism, Thiazoles/therapeutic use, Cell Adhesion Molecules
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