Inhibitory effects of regorafenib, a multiple tyrosine kinase inhibitor, on corneal neovascularization

<b>AIM:</b>To evaluate the inhibitory effects of regorafenib (BAY 73-4506), a multikinase inhibitor, on corneal neovascularization (NV).<b>METHODS:</b>Thirty adult male Sprague-Dawley rats weighing 250-300 g, were used. Corneal NV was induced by NaOH in the left eyes of each rat. Following the establishment of alkali burn, the animals were randomized into five groups according to topical treatment. Group 1 (<i>n </i>= 6) received 0.9% NaCl, Group 2 (<i>n </i>= 6) received dimethyl sulfoxide, Group 3 (<i>n </i>= 6) received regorafenib 1 mg/mL, Group 4 (<i>n </i>=6) received bevacizumab 5 mg/mL and Group 5 (<i>n </i>= 6) received 0.1% dexamethasone phosphate. On the 7d, the corneal surface covered with neovascular vessels was measured on photographs as the percentage of the cornea’s total area using computer-imaging analysis. The corneas obtained from rats were semiquantitatively evaluated for caspase-3 and vascular endothelial growth factor by immunostaining.<b>RESULTS:</b>A statistically significant difference in the percent area of corneal NV was found among the groups (<i>P </i>&lt;0.001). Although the Group 5 had the smallest percent area of corneal NV, there was no difference among Groups 3, 4 and 5 (<i>P </i>&gt;0.005). There was a statistically significant difference among the groups in apoptotic cell density (<i>P </i>= 0.002). The staining intensity of vascular endothelial growth factor in the epithelial and endothelial layers of cornea was significantly different among the groups (<i>P </i>&lt;0.05). The staining intensity of epithelial and endothelial vascular endothelial growth factor was significantly weaker in Groups 3, 4 and 5 than in Groups 1 and 2.<b>CONCLUSION:</b> Topical administration of regorafenib 1 mg/mL is partly effective for preventing alkali-induced corneal NV in rats

Serum and aqueous xanthine oxidase levels, and mRNA expression in anterior lens epithelial cells in pseudoexfoliation

Purpose: The aim of this study was to determine serum and aqueous xanthine oxidase (XO) levels, and mRNA expression in anterior lens epithelial cells in pseudoexfoliation (PEX). Methods: In this prospective study, serum, aqueous and anterior lens capsules were taken from 21 patients with PEX and 23 normal subjects who had undergone routine cataract surgery. Serum and aqueous XO levels were analyzed using the colorimetric method. mRNA expression of XO in anterior lens epithelial cells was evaluated using reverse transcription polymerase chain reaction analysis. Results: Serum XO levels (means ± standard deviations) were 207.0 ± 86.1 IU/mL and 240.6 ± 114.1 IU/mL in the normal and PEX groups, respectively (p = 0.310). Aqueous XO levels (means ± standard deviations) were 65.5 ± 54.3 IU/mL in the normal group and 130.5 ± 117.4 IU/mL in the PEX group (p = 0.028). There was a 2.9 fold decrease in mRNA expression in anterior lens epithelial cells of PEX, which is significantly lower than the normal group (p = 0.01). Conclusions: Higher aqueous XO levels lacking associated different serum XO suggests higher oxidative stress in the aqueous. Higher aqueous XO levels in PEX with decreased mRNA expression in anterior lens epithelial cells indicate possible overexpression of XO in other structures related to the aqueous. © 2015, Springer-Verlag Berlin Heidelberg