Inhibition of corneal neovascularization with bevacizumab eye drops in rabbits

Objective To investigate the effect of bevacizumab (Avastin) eye drops on inhibiting corneal neovascularization (CNV) induced by corneal alkali burn or suture in rabbits.Methods CNV was induced by alkali burn or suture in 27 rabbits respectively.Then the two groups were divided into Avastin eye drops,steroid eye drops,PBS control groups according to the treatments.Seven days after the alkali burn or suture injury,rabbits of each group received respective treatments,4 times a day for 14 days.On the 21st day,28th day,and 56th day after the injury,the area of CNV was examined;VEGF protein and mRNA expression in corneal tissues,VEGF protein expression in aqueous were detected by immunohistochemistry,RT-PCR and enzyme-linked immunosorbent assay (ELISA) respectively.Results CNV was significantly shorter and sparser in Avastin eye drops group and steroid eye drops group than that in PBS control group on the 21st day,28th day,and 56th day after the alkali burn.At three different time points,in Avastin eye drops group the area of CNV were (26.16±7.02) mm2,(29.71±10.43) mm2 and (26.10±10.72) mm2 respectively,which were significantly lower than that in PBS control group,there were all significant differences(all P0.01).On the 21st day,28th day,and 56th day after the suture injury,the area of CNV in Avastin eye drops group was (18.26±3.88) mm2,(37.24±3.16) mm2 and (40.16±3.38) mm2 respectively,which were significantly less than that in steroid eye drops group and PBS control group,there were all significant differences(all P0.01).In both models,VEGF protein expression in corneal epithelium in Avastin eye drops group more decreased markedly than that in PBS control group,with less neovascularization in stroma by immunohistochemistry on the 21st day after the alkali burn or suture injury.Results of RT-PCR showed that the expression of VEGF mRNA in corneal tissues in Avastin eye drops group was significantly lower than that in PBS control group on the 21st,28th day in both models,there were all significant differences (all P0.01),but on the 56th day the expression of VEGF mRNA in Avastin eye drops group and steroid eye drops group were both higher than that in PBS control group,there were all statistical differences (all P0.05).Results of ELISA showed that the VEGF protein content in the aqueous in Avastin eye drops group were (81.0±8.7)ng·L-1 and (110.0±9.02)ng·L-1 on the 21st day after the alkali burn and suture injury respectively,which were all significantly lower than that in steroid group and PBS control group,there were all significant differences(all P0.01).Conclusion The CNV induced by alkali burn or suture in rabbits can be effectively inhibited by Avastin eye drops,but the CNV area increases in the suture model after withdrawing Avastin eye drops,indicating the time of drugs treatment should be various according to the different cause of CNV.