title: Inhibition of placental growth factor improves surgical outcome of glaucoma surgery.
abstract: Excessive post-operative wound healing with subsequent scarring frequently leads to surgical failure of glaucoma filtration surgery (trabeculectomy). We investigated the hypothesis that placental growth factor (PlGF) plays a role in post-operative scar formation, and that it therefore may be a target for improvement of filtration surgery outcome. ELISA experiments showed that PlGF levels were significantly increased in aqueous humour of glaucoma patients and after VEGF treatment, which may indicate an important contribution of this growth factor to wound healing after trabeculectomy. Using a mouse model of glaucoma filtration surgery, we were able to show that intracameral injection of a previously characterized anti-PlGF antibody (ThromboGenics NV) significantly improved surgical outcome by increasing bleb survival and bleb area. This was associated with a significant reduction in post-operative proliferation, inflammation and angiogenesis during the first post-operative days after surgery, and with a decrease in collagen deposition at later stages. Furthermore, inhibition of PlGF seemed to be more effective than anti-VEGF-R2 treatment in improving surgical outcome, possibly via its additional effect on inflammation. These results render PlGF an appealing target for ocular wound healing and point to potential therapeutic benefits of PlGF inhibition for the prevention of surgical failure.
authors.affiliation: Laboratory of Ophthalmology, KU Leuven, Leuven, Belgium.
authors.forename: Tine
authors.initials: T
authors.lastname: Van Bergen
authors.forename: Bart
authors.initials: B
authors.lastname: Jonckx
authors.forename: Karolien
authors.initials: K
authors.lastname: Hollanders
authors.forename: Davine
authors.initials: D
authors.lastname: Sijnave
authors.forename: Sarah
authors.initials: S
authors.lastname: Van de Velde
authors.forename: Evelien
authors.initials: E
authors.lastname: Vandewalle
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Stassen
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Stalmans
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D001082:Aqueous Humor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002921:Cicatrix / Q000473:pathology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011817:Rabbits; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D058475:Tenon Capsule / Q000473:pathology; D014130:Trabeculectomy; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000906:Antibodies; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: PlGF; angiogenesis; fibrosis; glaucoma surgery; inflammation; wound healing