TY - JOUR T1 - Suppression and Regression of Choroidal Neovascularization by Systemic Administration of an α<sub>5</sub>β<sub>1</sub> Integrin Antagonist JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1820 LP - 1828 DO - 10.1124/mol.105.020941 VL - 69 IS - 6 AU - Naoyasu Umeda AU - Shu Kachi AU - Hideo Akiyama AU - Grit Zahn AU - Doerte Vossmeyer AU - Roland Stragies AU - Peter A. Campochiaro Y1 - 2006/06/01 UR - http://molpharm.aspetjournals.org/content/69/6/1820.abstract N2 - Integrin α5β1 plays an important role in developmental angiogenesis, but its role in various types of pathologic neovascularization has not been completely defined. In this study, we found strong up-regulation of α5β1 in choroidal neovascularization. Implantation of an osmotic pump delivering 1.5 or 10 μg/h (∼1.8 or 12 mg/kg/day) of 3-(2-{1-alkyl-5-[(pyridin-2-ylamino)-methyl]-pyrrolidin-3-yloxy}-acetylamino)-2-(alkylamino)-propionic acid (JSM6427), a selective α5β1 antagonist, caused significant suppression of choroidal neovascularization; the area of neovascularization was reduced by 33 to 40%. When an osmotic pump delivering 10 μg/h of JSM6427 was implanted 7 days after rupture of Bruch's membrane, there was terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining in vascular cells within the neovascularization and significant regression of the neovascularization over the next week. JSM6427 also induced apoptosis of cultured vascular endothelial cells. Fibronectin stimulates phosphorylation of extracellular signal-regulated kinase (ERK) in α5β1-expressing cells that is blocked by JSM6427. These data suggest that α5β1 plays a role in the development and maintenance of choroidal neovascularization and provides a target for therapeutic intervention. ER -