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T. van bergen, S. Van de Veire, L. Moons, I. Stalmans; Bevacizumab Can Reduce Wound Healing After Glaucoma Filtration Surgery by Inhibiting Vascular Density and Collagen Deposition. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3909.
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© ARVO (1962-2015); The Authors (2016-present)
Recently, we showed that vascular endothelial growth factor (VEGF) is involved in the process of wound healing after glaucoma filtration surgery. We showed that a single peroperative injection of bevacizumab (AvastinTM, Genentech) can improve surgical outcome in vivo in a rabbit model of trabeculectomy. The current study was designed to further elucidate the mechanisms of this inhibitory effect of bevacizumab on wound healing after filtering surgery.
The effect of bevacizumab on human umbilical vein endothelial cells (HUVEC) and Tenon fibroblasts in vitro was determined by using a proliferation assay. The effect of the monoclonal humanized antibody in vivo was investigated in a rabbit model of trabeculectomy by immunohistological analysis of angiogenesis (CD31), inflammation (CD45) and collagen deposition (Trichroom and Sirius Red). VEGF levels in aqueous humor samples were measured by ELISA.
VEGF was significantly increased in the aqueous humor samples of operated rabbits (895, 974, 716, 883, 858 and 854 pg/ml VEGF on days 1, 4, 6, 8, 14 and 30 postoperatively compared to 188 pg/ml 1 day prior to surgery, P<0.001). A single peroperative bevacizumab injection was able to reduce the VEGF-levels up to 4 days after surgery (750 and 588 pg/ml in bevacibumab-injected eyes versus 895 and 974 pg/ml VEGF in sham-injected eyeson days 1 and 4, P<0.05). A dose-dependent reduction of HUVEC and Tenon fibroblast proliferation was measured after bevacizumab administration in vitro (P<0.05 with a dose of at least 1 mg/ml bevacizumab for HUVEC and fibroblasts). In the in vivo model, the antibody reduced vascularity and collagen deposition. On day 3 after surgery, vascular density was decreased by 47% after treatment compared to sham injection. Collagen deposition was significantly reduced on day 14 (14%) and 30 (16%) after surgery compared to control.
This study shows that bevacizumab is able to improve glaucoma surgery outcome by reducing the process of wound healing. More specifically, bevacizumab-administration is able to inhibit not only angiogenesis, but also fibrosis, a very important process in wound healing. This study can open new perspectives for a safer and more efficient glaucoma surgery.
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