Angiopoietin-1 Suppresses Choroidal Neovascularization and Vascular Leakage

PURPOSE. To investigate the role of angiopoietin-1 (Ang1) in choroidal neovascularization (CNV) and vascular leakage. METHODS. We generated laser-induced CNV in mice and measured the size of CNV and vascular leakage after intravitreal administration of Ang1. The expressions and distributions of endothelial junctional proteins were analyzed using immunohistochemistry and Western blot. Moreover, we compared the sizes of CNV and vascular leakage in Ang1-overexpressing, Ang1-deficient, and their littermate control mice. In addition, following the transplantation of GFP(+) bone marrow cells into these Ang1-genetically modified mice, we evaluated the recruitment of VEGF-A producing macrophages from the bone marrow after CNV induction. RESULTS. Intravitreal administration of Ang1 was as effective as VEGF-Trap in inhibiting CNV formation. Furthermore, Ang1 suppressed vascular leakage by increasing endothelial junctional proteins, which was more effective than VEGF-Trap. Genetic deletion of Ang1 exacerbated, while overexpression of Ang1 suppressed CNV formation and vascular leakage. We attribute these Ang1-induced, anti-angiogenic, and anti-leakage effects to its inhibitory actions against the recruitment and infiltration of VEGF-A-producing macrophages from bone marrow into the inflammatory lesions. CONCLUSIONS. Ang1 supplementation can be established as a therapeutic strategy to suppress the CNV formation and vascular leakage by inhibiting the recruitment of angiogenic macrophages and tightening the endothelial junctions.