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

BackgroundTo evaluate the effects of bevacizumab eye drops on corneal epithelial wound healing and the stromal response after epithelial injury in rats. MethodsWe 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. ResultsThe 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- (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. ConclusionsThe bevacizumab eye drops delay the wound healing and increase stromal response after corneal epithelial injury in rats.