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Originally published In Press as doi:10.1167/iovs.08-2662 on May 27, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:5217-5225.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2662
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Inhibition of Vascular Endothelial Growth Factor Reduces Scar Formation after Glaucoma Filtration Surgery

Zhongqiu Li,1,2,3 Tine Van Bergen,1,2 Sara Van de Veire,1,4 Isabelle Van de Vel,1 Huberte Moreau,5 Mieke Dewerchin,6 Prabhat C. Maudgal,4 Thierry Zeyen,4 Werner Spileers,1,4 Lieve Moons,7 and Ingeborg Stalmans1,4

From the 1Laboratory of Ophthalmology, and 7Department of Biology, Catholic University Leuven, Leuven, Belgium; 4Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium; 5ThromboGenics NV, Leuven, Belgium; 6Vesalius Research Center, Flanders Interuniversity Institute of Biotechnology (VIB), Leuven, Belgium; and 3Department of Ophthalmology, Chao-yang Hospital, Capital Medical University, Beijing, P.R. China.

Corresponding author: Ingeborg Stalmans, University Hospitals Leuven, Department of Ophthalmology, Kapucijnenvoer 33, B-3000, Leuven, Belgium; ingeborg.stalmans{at}uz.kuleuven.be.

Purpose. Filtration failure due to excessive postoperative scarring remains a major problem after glaucoma surgery. The authors have investigated whether glaucoma and filtration surgery are associated with increased levels of vascular endothelial growth factor (VEGF), and whether a humanized monoclonal antibody against VEGF, bevacizumab, can reduce postoperative scar formation and improve surgical outcome.

Methods. The levels of VEGF in samples of aqueous humor were measured by ELISA. The expression of the VEGF receptors Flt-1 and KDR was analyzed in cultured Tenon fibroblasts by real-time RT-PCR and Western blotting. The effect of VEGF and bevacizumab on Tenon fibroblasts in vitro was determined using a proliferation assay. The in vivo effect of the antibody was investigated in a rabbit model of trabeculectomy by measuring the intraocular pressure (IOP) and bleb area, and by immunohistological analysis of angiogenesis, inflammation, and fibrosis.

Results. VEGF levels were increased significantly in the aqueous humor of glaucoma patients and rabbits that had undergone surgery. Both VEGF receptors were expressed on Tenon fibroblasts. Fibroblast proliferation in vitro was stimulated by delivery of VEGF, and was inhibited by administration of bevacizumab. The antibody also reduced angiogenesis and collagen deposition significantly, and improved the outcome of glaucoma surgery in rabbits.

Conclusions. VEGF was upregulated in the aqueous humor of glaucoma patients and in the rabbit model, and it stimulated fibroblast proliferation in vitro. This suggests that it is involved in the scarring process after filtration surgery. Bevacizumab reduced the proliferation of fibroblasts in vitro and improved surgical outcome.






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