Retinoic acid receptor agonist Am90 inhibits experimental choroidal neovasucularization

Abstract

Abstract: : Purpose: All–trans retinoic acid (ATRA) and other retinoids are reported to inhibit angiogenesis and vascular endothelial cell differentiation and migration. We investigated the effect of the synthetic retinoid acid derivative Am90, a selective retinoic acid receptor(RAR) agonist, on experimentally induced choroidal neovascularization(CNV). Methods: Murine model of choroidal neovascularzation was created in C57BL6/J mice by diode laser photocoagulation to the bilateral fundi (6 lesions: 400mW in power; 0.05msec in duration, 50mm in size). Mice were assigned to two groups receiving daily oral adiministration of 5mg/kg of Am80(n=11) or the vehicle(n=8). Fluorescein angiography (FA) was performed on day 7 and the degree of fluorescein leakage from the photocoagulated lesions was graded on a scale of 0–3 (0:no leakage; 1: slight leakage; 2:moderate leakage; 3: prominent leakage). The eyes were enucleated for subsequent histopathological analysis of the fibrovascular membrane. Results: Fluroescein leakage score was 20% lower in Am80 treated group compared with the control group (p<0.01), and the fibrovascular membranes formed in the Am80 treated group were 35% smaller in size (p<0.05). Discussion: In our murine model of experimentally induced CNV, Am80 inhibited the formation of CNV. Our results demonstrate that retinoids may be a promising therapy for CNV.

Keywords: age–related macular degeneration • pathology: experimental • pharmacology