Direct Effects of Bevacizumab on Rat Conjunctival Fibroblast

Abstract

Successful cases of treatment of Bevacizumab for preventing scar after trabeculectomy in glaucoma patients encourage us to explore its mechanism. In this study, we primarily isolated conjunctival fibroblast from rat. RT-PCR analysis for the cells implicated that conjunctival fibroblast expressed vascular endothelial growth factor (VEGF) and its receptors. Immunofluorescence staining also showed positive staining for VEGFR-1. Furthermore, growth of fibroblast was significantly inhibited by Bevacizumab at dose of 2.5 mg/ml. Real time PCR results showed after 48 h intervention of 2.5 mg/ml Bevacizumab, the mRNA expressions of VEGF and its receptors decreased compared to the control group (P < 0.05) and Bevacizumab also decreased expression of TGFβ1 and TGFβ2 (P < 0.05). In summary, our finding demonstrated that Bevacizumab could directly act on fibroblast and inhibit VEGF, TGFβ1, and TGFβ2 expression.

Bevacizumab Promotes T-Cell–Mediated Collagen Deposition in the Mouse Model of Conjunctival Scarring

“…[21][22][23][24] The in vivo mechanism(s) for the observed antifibrotic property of bevacizumab is unclear, although these laboratory studies implicated the capacity of bevacizumab to inhibit fibroblast proliferation as well as reduce expression of profibrotic TGF-b and collagen deposition as reasons behind the improved experimental surgical outcomes. 21,[24][25][26][27] To add to the confusion, a growing number of reports from clinical trials evaluating the effect of anti-VEGF-A therapies, including bevacizumab, on AMD, DR, as well as myopic choroidal neovascularization, have begun describing an association between this form of treatment and scar formation. [28][29][30][31][32][33][34][35][36][37][38][39][40][41] These observations suggest that repeated intravitreal injections of anti-VEGF-A therapies may, in fact, increase the risk of ocular scarring, a major factor leading to sustained loss of visual acuity.…”