The effects of topical everolimus and sunitinib on corneal neovascularization

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PURPOSE: To evaluate the effects of topical everolimus and sunitinib on corneal neovascularization (CNV). METHODS: CNV was induced by application of silver nitrate to the cornea for all groups. Rats were divided into four groups of 10 rats each, and two corneas were obtained from each rat. Group I received 1 mg/ml everolimus, Group II received 0.5 mg/ml sunitinib, Group IV received no treatment (control group) and Group IV received 1% Dimethylsulfoxide (DMSO). All treatments were administrated twice daily for 2 weeks. The right corneas were used for extracellular signal-regulated kinase 1/2 (ERK 1/2) protein analysis by western blot analysis and the left corneas were used for ERK 1/2 and vascular endothelial growth factor-receptor (VEGFR-2) gene expression analysis by quantitative real-time PCR. RESULTS: VEGFR-2 mRNA expression levels (ΔCt, median, min-max) were reduced in the everolimus 1.0 (0.25-1.81) and sunitinib 1.06 (0.24-2.68) treated groups compared with the control 4.74 (1.02-14.74) and DMSO groups 7.41 (0.72-13.10). The expression of ERK 1/2 protein and mRNA levels were reduced in everolimus group compared with the control group (p < 0.05). These differences were not seen between the sunitinib and control groups. CONCLUSION: Topical administration of both everolimus and sunitinib reduced VEGFR-2 levels and inhibited CNV. In additon, everolimus reduced ERK 1/2 levels and seems to be more effective than sunitinib on CNV.