Abstract
Purpose::
To assess the potential beneficial effects of gliclazide and other sulphonylureas on diabetic retinopathy using a murine model of ischemia-induced retinal neovascularization.
Methods::
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.
Results::
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).
Conclusions::
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.
Keywords: retinal neovascularization • antioxidants