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Tine Van Bergen, Bart Jonckx, Sarah Van de Velde, Karolien Hollanders, Davine Sijnave, Evelien Vandewalle, Lieve K. Moons, Jean-Marie Stassen, Ingeborg Stalmans; Targeting Placental Growth Factor (PlGF) with an Inhibitory Monoclonal Antibody (5D11D4): New Therapeutic Approach for Glaucoma Filtration Failure. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6352.
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Excessive postoperative wound healing with subsequent inflammation and scarring frequently leads to surgical failure of glaucoma filtration surgery (GFS). We intend to check the hypothesis that placental growth factor (PlGF) plays a role in scar formation after GFS, and that it may be a target for improvement of the outcome of this surgery.
Aqueous humor and plasma samples of glaucoma and control patients (n=10) were collected and PlGF levels were determined by ELISA. 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 intra-ocular pressure (IOP), bleb area and bleb survival every other day. All antibodies were kindly provided by ThromboGenics NV.
PlGF levels in aqueous humor were found to be significantly upregulated in glaucoma compared to control patients (17 ± 2 pg/ml versus 12 ± 0.75 pg/ml, p=0.03). No significant differences were found in plasma concentrations of PlGF. 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). IOP was not found to be significantly different in any of the groups (p>0.05).
Local production of PlGF in the eye may indicate an important role for this growth factor in wound healing after GFS. Indeed, 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.
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