Placental growth factor (PlGF) inhibition reduces choroidal neovascularization in a mouse model for age‐related macular degeneration

Abstract Purpose: To evaluate whether and through which mechanism PlGF blockage can inhibit choroidal neovascularization (CNV) in a mouse model of age‐related macular degeneration (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, 144 wild‐type mice were injected every 2 days with 5, 10, 20 or 40 mg/kg of either an anti‐PlGF‐antibody, an anti‐VEGF receptor‐2 (VEGFR2) antibody or an irrelevant control antibody. The CNV lesions were evaluated on histological cross‐sections. The amount of endothelial cells, pericytes and inflammatory cells in the lesions were morphometrically analyzed after immunostaining for CD31, smooth muscle alpha‐actin and F4/80 respectively. Results: CNV formation was significantly reduced in the PlGF knockout mice. The dose‐response experiment showed that the 20 mg/kg dose of anti‐PlGF significantly reduced the number of vessels in the lesions as compared to control antibody (p= 0.045), although less than a comparable dose of anti‐VEGFR2 (p=0.027). Moreover, smooth muscle cell coverage was significantly increased in the anti‐PlGF treated (p=0.04) and reduced in the anti‐VEGFR2 treated mice (p=0.03) as compared to control mice. Finally, a significant reduction in number of inflammatory cells was observed in the lesions treated with anti‐PlGF (p=0.017) but not in the anti‐VEGFR2 treated mice (p=0.33). Conclusions: Anti‐PlGF treatment inhibits CNV formation in a mouse model for ARMD. Both anti‐PlGF and anti‐VEGFR2 impair capillary growth, but in contrary to VEGFR2 blockage, anti‐PlGF also reduces inflammation and promotes vessel maturation.