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

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.

Citation

Tetsushi Kimura, Hitoshi Takagi, Kiyoshi Suzuma, Mihori Kita, Daisuke Watanabe, Nagahisa Yoshimura. Comparisons between the beneficial effects of different sulphonylurea treatments on ischemia-induced retinal neovascularization. Free radical biology & medicine. 2007 Aug 1;43(3):454-61

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PMID: 17602961

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