Comparisons between the beneficial effects of different sulphonylurea treatments on ischemia-induced retinal...

The aim of this study was to assess the potential beneficial effects of gliclazide and other sulphonylureas on ischemia-induced retinal neovascularization. To produce an animal model of oxygen-induced ischemic retinopathy, 7-day-old (P7) mice were exposed to a 75% oxygen environment for 5 days. On their return to ambient air at P12, these mice were then treated with gliclazide, glibenclamide, glimepiride, or N-acetylcysteine. Gliclazide, but not glibenclamide or glimepiride, markedly suppresses retinal neovascularization. N-Acetylcysteine, however, only moderately suppresses retinal neovascularization. The number of neovascular nuclei in the retinal cross sections decreased by 29% in the gliclazide-treated mice (P<0.05 vs control). The induction of VEGF mRNA expression at P13 is significantly suppressed in the gliclazide group, relative to the control group (-44%, P<0.05). The VEGF protein expression levels at P15 were also suppressed in the gliclazide group (-43%, P<0.01). The 8-isoprostane production levels at P15 were suppressed in both the gliclazide group (-20%, P<0.05) and the N-acetylcysteine-treated group (-31%, P<0.01). Gliclazide inhibits ischemia-induced retinal neovascularization, and this is likely to be mediated in part through the downregulation of VEGF and the suppression of oxidative stress.