Abstract
Purpose: :
Integrin α5ß1 plays an important role in developmental angiogenesis, but its role in various types of pathologic neovascularization has not been completely defined.
Methods: :
The effect of JSM6427, a selective α5ß1 antagonist, was quantitatively assessed in mice with choroidal neovascularization due to laser–induced rupture of Bruch's membrane.
Results: :
In this study, we found strong upregulation of α5ß1 in choroidal neovascularization. Implantation of an osmotic pump delivering 1.5 or 10 µ/hour (∼1.8 or 12 mg/kg/day) of JSM6427 caused significant suppression of choroidal neovascularization; the area of neovascularization was reduced by 33 to 40%. When an osmotic pump delivering 10 µg/hour of JSM6427 was implanted 7 days after rupture of Bruch's membrane, there was TUNEL staining in vascular cells within the neovascularization and significant regression of the neovascularization over the next week.
Conclusions: :
These data suggest that α5ß1 plays a role in the development and maintenance of choroidal neovascularization and provides a target for therapeutic intervention.
Keywords: choroid: neovascularization • drug toxicity/drug effects