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T. Kimura, H. Takagi, K. Suzuma, D. Watanabe, M. Kita, N. Yoshimura; The Beneficial Effects of Free Radical Scavenging Upon Ischemia-Induced Retinal Neovascularization: Comparisons Between Different Sulphonylurea Treatments. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3404.
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To assess the potential beneficial effects of gliclazide and other sulphonylureas on diabetic retinopathy using a murine model of ischemia-induced retinal neovascularization.
To induce ischemia-induced retinal neovascularization, 7-day-old (P7) mice were exposed to a 75% oxygen environment for 5 days, followed by a return to ambient air. At this timepoint (P12), the mice were divided into four groups comprising an untreated group (control), and gliclazide- (150mg/kg/day), glibenclamide- (8.6mg/kg/day), and glimepiride- (7mg/kg/day) treated groups. Retinal vasculature was then examined and vascular endothelial growth factor (VEGF) mRNA was quantified.
Gliclazide, but not glibenclamide or glimepiride, markedly suppresses retinal neovascularization in P17 mice. The numbers of neovascular nuclei were 55.2±2.6 in the control group, 38.9±2.9 in the gliclazide group (P<0.05 vs. control group), 52.4±3.5 in the glibenclamide group, and 59.6±3.2 in the glimepiride group. Real-time quantitative RT-PCR analyses further revealed that the induction of VEGF mRNA expression is significantly suppressed in the gliclazide group only, relative to the control group (-44%, P<0.05).
Gliclazide inhibits ischemia-induced retinal neovascularization events and this is possibly in part mediated through the downregulation of VEGF. Gliclazide treatment might therefore prove to be a novel therapeutic strategy in the treatment of diabetic retinopathy.
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