Bevacizumab and motesanib effect on experimental corneal neovascularization model

The cornea with its transparent and avascular structure is necessary to provide a suitable anterior refractive surface. Maintaining corneal avascularity is a vital feature of corneal physiology. Corneal neovascularization, which may occur as a result of physical, chemical or pathological traumas, can lead to functionally severe vision loss with irreguler optical surface, weakened tensile strength and inadequate barrier function. The aim of our study; comparison of the efficacy of topical Bevacizumab and topical Motesanib in experimental corneal neovascularization model through quantitative Real-Time PCR (qRT-PCR) method, VEGF-A mRNA, VEGFR-2 mRNA and microRNA expression levels that are predicted to be used as biomarkers and determining the most effective dose of topical Motesanib. 42 Wistor Albino rats were randomly divided into six groups with an equal number of rats in each group. Corneal cauterization was applied to all groups except the control group. Group I (control) did not receive any treatment. Group II (sham) were applied DMSO 3 times a day. Group III were applied 5 mg/ml topical Bevacizumab drops to 3 times a day. Topical Motesanib drops of 2.5 mg/ml were applied to group IV, 5 mg/ml to group V, and 7.5 mg/ml to group VI, 3 times a day. After seven days of treatment, corneal photographs of all rats were taken under general anesthesia. The ratio of neovascularization areas to the entire corneal surface was determined. The corneas were excised with a 4 mm punch under the operating microscope, then the rats were decapitated. VEGF-A mRNA, VEGFR-2 mRNA, miRNA-21, miRNA-27a, miRNA-31, miRNA-126, miRNA-184 and miRNA-204 parameters were evaluated by qRT-PCR method in the removed corneas. The percentage of corneal neovascularization areas to the entire cornea was lower in the treatment groups compared to the DMSO group. VEGF-A mRNA levels in all treatment groups; It was found to be statistically significantly decreased compared to the control group and the DMSO group (p<0.05). There was no significant difference between the treatment groups (p>0.05). VEGFR-2 mRNA expression levels in all treatment groups; It was observed that it decreased compared to the control group and DMSO group. Among the treatment groups, there was a statistically significant decrease in VEGFR-2 mRNA expression level in the Motesanib 7.5 mg/ml group compared to the other treatment groups (Bevacizumab 5 mg/ml, Motesanib 2.5 mg/ml, Motesanib 5 mg/ml) (respectively; p=0.016, p=0.046 and p=0.015) In addition, statistically significant changes were detected in the expression levels of only miRNA-126 among the miRNAs evaluated in the study. No significant change was observed between the treatment groups. In conclusion, motesanib can be used as a new agent in the treatment of corneal neovascularization because it reduces the levels of VEGF-A mRNA and VEGFR-2 mRNA, which are corneal neovascularization markers. The fact that Motesanib 7.5 mg/ml suppressed VEGFR-2 mRNA level at a statistically significant level compared to other treatment doses and Bevacizumab 5 mg/ml suggests that it may be more effective than Bevacizumab and its dose-dependent effectiveness may increase. In addition, we think that miRNA-126, whose significant changes were detected among the miRNAs evaluated in the study, can be used as a proangiogenic genetic marker. Further studies are needed to evaluate the efficacy and safety of motesanib on corneal neovascularization.