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K. Mori, A. Kakehashi, N. Kinoshita, H. Yamagami, M. Kawakami, Y. Kanazawa; Prevention of Diabetic Retinopathy in Spontaneously Diabetic Torii Rats by a Sulfonylurea, Gliclazide, Independent of Blood Glucose Level . Invest. Ophthalmol. Vis. Sci. 2005;46(13):429.
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Purpose: We reported that gliclazide, a sulfonylurea, improves retinal leukostasis independent of blood glucose level in the streptozotocin–induced early diabetic retinopathy rat model (Diabetologia 2002). In the present study, we evaluated the effects of gliclazide on the development of diabetic retinopathy (DR) in spontaneously diabetic Torii (STD) rats, which develop severe diabetic ocular complications (Int J Experimental Diab Res 2000). Methods: Gliclazide or glibenclamide, sulfonylureas, was mixed with bait and administered orally after diabetes progressed in the SDT rats. The rats were divided into three groups: the 0.2% gliclazide–treated group (n=7; mean age, 58 weeks), the 0.4% gliclazide–treated group (n=4; mean age, 60 weeks), and the 0.0125% glibenclamide–treated group (n=7; mean age, 58 weeks). DR was evaluated in vivo by fluorescein angiomicroscopy. When extensive hyperfluorescence around the optic disc associated with vascular tortuosity was observed, the rat was confirmed to have DR. Results: The fasting blood glucose level at sacrifice was over 600 mg/dl in all rats except for one rat (330 mg/dl). DR was observed by fluorescein angiomicroscopy in 1/7 eyes (14%) in the 0.2% gliclazide–treated group, 0/4 eyes (0%) in the 0.4% gliclazide–treated group, and 4/7 eyes (57%) in the 0.0125% glibenclamide–treated group. Although there was no significant difference in progression of DR among the groups, the 0.2% gliclazide–treated group and the 0.4% gliclazide–treated group (n=11) considered together had less progression of DR (1/11 eyes, 9%) compared with the 0.0125% glibenclamide–treated group (4/7 eyes, 57%) (p=0.047). Conclusions:Treatment with gliclazide decreased the prevalence of DR in SDT rats independent of the blood glucose level. The extrapancreatic action of gliclazide, i.e., antioxidant, anti–retinal leukostasis, and anti–VEGF effects, might have a therapeutic effect on the development of DR.
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