Effect of bevacizumab and ramucirumab on TRPM2 and VEGF immunereactivity in 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; To investigate the efficacy of topical Bevacizumab and topical Ramucirumab in an experimental corneal neovascularization model, to investigate the effects of these two drugs on TRPM2 and VEGF immunoreactivity, and to determine the most effective dose of topical Ramucirumab. 42 Sprague Dawley rats were randomly divided into six groups with an equal number of rats in each group. All right corneas of rats cotherized with silver nitrat except control group. Group I (control) did not receive any treatment. Group II (sham) were applied DMSO 2 times a day. Group III were applied 5 mg/ml topical Bevacizumab drops to 2 times a day. Topical Ramucirumab drops of 2.5 mg/ml were applied to group IV, 5 mg/ml to group V, and 10 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 percentage of the corneal surface covered with new vessels to the entire corneal area was measured and compared. On the 14th day, decapitation was performed under anesthesia and the eyes were enucleated. Histoscoring was performed by performing VEGF, VEGFR-2, TRPM2 and TUNEL staining immunostaining in the cornea. TAS and TOS values were checked from the blood sample taken on the 14th day. The percentage of corneal neovascularization areas to the entire cornea was lower in the treatment groups compared to the CNV group. It was observed that the immunoreactivity of VEGF, VEGFR-2 and TRPM2 was statistically significantly increased in the CNV group compared to the control group, A statistically significant decrease was observed in the treatment groups compared to the CNV group, but there was no statistically significant difference between the treatment groups. When TUNEL positivity was compared with the control group, a statistically significant increase was observed in the CNV group, A statistically significant decrease was observed in the treatment groups compared to the CNV group, but there was no statistically significant difference between the treatment groups. When serum TAS levels were compared with the control group, it was observed that there was a statistically significant decrease in the CNV group, It was observed that there was a statistically significant increase in the treatment groups compared to the CNV group, but there was no statistically significant difference between the treatment groups. When serum TOS levels were compared with the control group, it was observed that there was a statistically significant increase in the CNV group, A statistically significant decrease was observed in the treatment groups compared to the CNV group, but there was no statistically significant difference between the treatment groups. As a result, Ramucirumab decreased the levels of corneal neovascularization marker VEGF and VEGFR-2; It can be used as a new agent in the treatment of corneal neovascularization. In addition, due to the significant change in TRPM2 evaluated in the study, we think that TRPM2 may be a new proangiogenic factor in corneal neovascularization and ramucirumab may be a new agent in the treatment of CNV, supported by further studies. Keywords: Corneal neovascularization, Bevacizumab, Ramucirumab