Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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.
Conclusions: :
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.
Keywords: vascular endothelial growth factor • wound healing