Inhibition of placental growth factor improves surgical outcome of glaucoma surgery

Purpose We checked the hypothesis that placental growth factor (PlGF) plays a role in scar formation after glaucoma filtration surgery (GFS), and that it may be a target for improvement of the outcome of this surgery. Methods The effect of the anti-murine PlGF-antibody (5D11D4) was investigated in a mouse model of GFS in C75Bl/6 mice. Immediately after surgery 5D11D4 (1µl; 5.2mg/ml) or 1C8, an irrelevant mouse IgG antibody (1µl; 4.8 mg/ml), was injected in the anterior chamber (n=10 eyes for both groups). An anti-murine VEGF-R2 antibody (DC101) was used as a positive control (1µl; 6.2 mg/ml; n=10). Mice were killed on post-operative day 8. Treatment outcome was studied by clinical investigation of bleb area and bleb survival every other day. All antibodies were kindly provided by ThromboGenics NV. Results In the mouse model of GFS, treatment using the anti-PlGF antibody (5D11D4) significantly improved surgical outcome by increasing bleb survival (p=0.04) and bleb area (p=0.01) with 29% compared to negative control (1C8). A single administration of anti-VEGF-R2 (DC101) also significantly improved bleb area with 7% as compared to 1C8 (p=0.05), but had no effect on bleb survival (p=0.23). A trend towards an increased bleb area after 5D11D4 administration was observed compared to DC101 delivery (p=0.07). Conclusion Targeting PlGF with an inhibitory monoclonal antibody is efficacious in improving GFS outcome, possibly even more effectively than inhibition of VEGF-R2. These results render PlGF an appealing target for ocular wound healing and point to the potential therapeutic benefits of PlGF-inhibition.