Bevacizumab eye drops delay corneal epithelial wound healing and increase the stromal response to epithelial injury in rats

Background: To evaluate the effects of bevacizumab eye drops on corneal epithelial wound healing and the stromal response after epithelial injury in rats. Methods: We divided 160 Sprague-Dawley male rats into two groups and de-epithelized corneas with a microblade. Five percent bevacizumab (Avastin) and antibiotic (Cravit) eyedrops were treated four times daily in the bevacizumab group and antibiotic eye drops only in the control group. Wound area evaluation, enzyme-linked immunosorbent assay, immunofluorescent staining, and real-time polymerase chain reaction were performed with rat corneas. Results: The percentage of wound healing in the bevacizumab group was lower than in the control group at 24, 48 and 72 hours after epithelial debridement (P=0.02, 0.01 and 0.01). Corneal matrix metalloproteinase-2 (P=0.02, 0.01 and 0.02), matrix metalloproteinase-9 (P=0.03, 0.01 and 0.01) and transforming growth factor-β (P=0.02, 0.02 and 0.01) proteins in the bevacizumab group were higher than control group at 24, 48, and 72 hours. Matrix metalloproteinase-2, matrix metalloproteinase-9, transforming growth factor-b and a-smooth muscle actin were strongly stained in the bevacizumab corneas compared with control corneas in immunofluorescent staining. Matrix metalloproteinase-2 (P=0.04, 0.03 and 0.04), matrix metalloproteinase- 9 (P=0.03, 0.01 and 0.02), transforming growth factor-b (P=0.03, 0.03 and 0.03) and a-smooth muscle actin (P=0.04, 0.01 and 0.04) messenger RNA levels in the bevacizumab group were also highly expressed compared with the control group at 24, 48, and 72 hours. Conclusions: The bevacizumab eye drops delay the wound healing and increase stromal response after corneal epithelial injury in rats.