Title | Inhibition of Vascular Endothelial Growth Factor Reduces Scar Formation after Glaucoma Filtration Surgery |
Purpose | In 30-50% of cases, glaucoma filtration surgery fails due to excessive post-operative scarring. In this study, we investigated whether glaucoma and filtration surgery are associated with increased levels of vascular endothelial growth factor (VEGF) and whether the humanized monoclonal VEGF-antibody bevacizumab (AvastinTM, Genentech) can reduce post-operative scar formation and improve surgical outcome. |
Methods | VEGF levels in aqueous humor samples were measured by ELISA. Expression of VEGF-receptors Flt-1 and KDR was analyzed in cultured Tenon fibroblasts by real-time RT-PCR and Western blot. The effect of VEGF and bevacizumab on Tenon fibroblasts in vitro was determined using a proliferation assay. The effect of the antibody in vivo was investigated in a rabbit trabeculectomy model by measuring the intra-ocular pressure (IOP) and the bleb area and by immunohistological analysis of vascularity, inflammation and fibrosis. |
Results | VEGF was significantly increased in the aqueous humor of glaucoma patients as well as in operated rabbits. Both VEGF-receptors were expressed on Tenon fibroblasts. The proliferation of Tenon fibroblasts in vitro was significantly stimulated by VEGF-delivery and inhibited by bevacizumab-administration. The antibody also significantly reduced vascularity and collagen deposition and improved glaucoma surgery outcome. |
Conclusion | VEGF is up-regulated in aqueous humor of glaucoma patients and operated rabbits and stimulates in vitro fibroblast proliferation, suggesting that it plays a role in the scarring process after filtration surgery. Bevacizumab reduces in vitro fibroblast proliferation and improves in vivo surgical outcome. |
Last name | VAN BERGEN |
Initials | TVB |
Department | KUL |
City | Leuven |
Last name | VAN DE VEIRE |
Initials | SVDV |
Department | KUL |
City | Leuven |
Last name | MOONS |
Initials | LM |
Department | KUL |
City | Leuven |
Last name | STALMANS |
Initials | IS |
Department | KUL |
City | Leuven |