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Blockade of vascular adhesion protein-1 attenuates choroidal neovascularization
- Source :
- Molecular vision. 18:593-600
- Publication Year :
- 2012
- Publisher :
- Molecular Vision, 2012.
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 10900535
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Molecular vision
- Accession number :
- edsair.jairo.........dbd91fc75e6eeb53447d1920c1ae3a4b