Anti-PlGF (Placental Growth Factor) Reduces Choroidal Neovascularization in a Mouse Model of Age-Related Macular Degeneration (ARMD)

Abstract

Purpose: : To evaluate whether and through which mechanism PlGF blockage can inhibit choroidal neovascularization (CNV)in a mouse model of ARMD.

Methods: : CNV was induced in mice by placing 3 Argon laser burns on the choroid. In a first experiment we compared CNV formation between PlGF knock-out and wild type mice. Secondly, wild-type mice were injected intraperitoneally with 6, 12, 25 or 50 mg/kg of either an anti-PlGF-antibody, an anti-VEGF receptor-2 (VEGFR2) antibody, a combination of both or an irrelevant control antibody. The CNV lesions were evaluated on flat mounts and histological cross-sections. The amount of endothelial cells and inflammatory cells in the lesions was morphometrically analyzed after immunostaining for CD31 or F4/80 respectively. Thirdly, combination therapy with anti-PlGF and anti-VEGF receptor-2 was given to seek for additional inhibition of neovascularization.

Results: : CNV formation was significantly reduced in PlGF knockout mice. Anti-PlGF significantly inhibited choroidal neovascularization, comparably to anti-VEGFR2 (p<0.05). Moreover, a combination treatment of anti-PlGF and anti-VEGFR2 further suppressed CNV (p<0.05). Finally, a significant reduction in the number of inflammatory cells was observed in the lesions treated with anti-PlGF (p<0.05), but not in anti-VEGFR2 treated mice.

Keywords: age-related macular degeneration • choroid: neovascularization • growth factors/growth factor receptors