Anti‐PlGF (placental growth factor) as a safer alternative for anti‐VEGF in the treatment of age‐related macular degeneration (AMD)?

Abstract Purpose To evaluate the efficacy and safety of PlGF blockage by inhibiting choroidal neovascularization (CNV) in a mouse model of AMD. Methods A laser‐induced CNV model was used in C57Bl/6 mice. Mice were injected intraperitoneally with 25 mg/kg of an anti‐PlGF‐antibody, an anti‐VEGF receptor2 (VEGFR2) antibody, a combination of both, or a control antibody. The CNV lesions were evaluated on flat mounts and serial sections after 14 days, by immunostainings for endothelial and inflammatory cells (CD31 and F4/80 respectively). Ganglion cell survival was scored via NeuN and TUNEL staining after 2, 4, and 6 weeks in C57Bl/6 and Swiss mice with and without CNV lasering. Safety of anti‐PlGF and anti‐VEGFR2 on normal vascular development in the retina, kidney, and heart was assessed. Results Anti‐PlGF or anti‐VEGFR2 comparably inhibited CNV by ± 50%. Moreover, a combination treatment of the optimal dose of anti‐PlGF and a lower dose of anti‐VEGFR2 further suppressed CNV to ± 70%, allowing to reduce the dose of anti‐VEGFR2 by fourfold. Anti‐PlGF did not inhibit vascular development in the retina, heart, or kidney, whereas a reduction of ± 40% was seen after anti‐VEGFR2 treatment. Repeated anti‐VEGFR2 injections induced an increase in ganglion cell apoptosis after 4 and 6 weeks of administration, whereas anti‐PlGF did not. Conclusion Anti‐PlGF treatment inhibits CNV formation in a mouse model of AMD, and enhances the efficacy of anti‐VEGFR‐2, allowing the dose of anti‐VEGF therapy to be lowered and the potential adverse effects to be minimized. Moreover and contrary to anti‐VEGFR2, anti‐PlGF is safe for the neuroretina and for the systemic and retinal vascular development.