PT  - JOURNAL ARTICLE
AU  - Naoyasu Umeda
AU  - Shu Kachi
AU  - Hideo Akiyama
AU  - Grit Zahn
AU  - Doerte Vossmeyer
AU  - Roland Stragies
AU  - Peter A. Campochiaro
TI  - Suppression and Regression of Choroidal Neovascularization by Systemic Administration of an α<sub>5</sub>β<sub>1</sub> Integrin Antagonist
AID  - 10.1124/mol.105.020941
DP  - 2006 Jun 01
TA  - Molecular Pharmacology
PG  - 1820--1828
VI  - 69
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/69/6/1820.short
4100  - http://molpharm.aspetjournals.org/content/69/6/1820.full
SO  - Mol Pharmacol2006 Jun 01; 69
AB  - 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.