Abstract 3720: New Experimental Model of Type 2 Diabetes in Rabbits Promotes Retina Microaneurisms, which are Attenuated by Renin-Angiotensin Blockade
Type 2 diabetes is responsible for macro- and microvascular complications, including cardiovascular disease, nephropathy and retinopathy. We present a new animal model for the study of the retina effects of experimental type 2 diabetes and to verify if reninangiotensin (RA) blockade can attenuate this process. Diabetes and hypercholesterolemia were induced in New Zealand white male rabbits by a high-fat/high-sucrose (10/40%) and cholesterol-enriched diet (0.5% for 12 weeks, followed by 0.1% up to end of study), maintained for 24 weeks. Animals were randomized to receive diet alone (GII, n=10), quinapril 30 mg (GIII, n=8), or olmesartan 5 mg (GIV, n=8) added to the diet during the study protocol. GI (n=4) were normal controls. Fasting serum lipids and plasma glucose levels were examined at baseline, 12 and 24 weeks. Fundus photographs and fluorescein angiography were performed at 12 and 24 weeks, with microaneurisms (An) determined on standard photographs, with radius equivalent to the diameter of the average optic disc, considering the area within 1500 micra of the border of the optic disc. The number of An was analyzed and the animals were graded into 4 levels: I < 10; II 11–30; III 31– 40; IV > 40 An. In this animal model we observed similar body weight gain. TC and LDL-C were markedly increased from the first month on (p<0.001), whereas hyperglicemia appeared 6 months after induction (316.3 +/− 127.2 mg/dL, p<0.05 vs. baseline), w/o differences regarding treatment assignment. At week 12, diabetic rabbits exhibited early clinical features of retinopathy, including hyperfluorescent dots consistent with An. The degree of retinopathy was attenuated with RA blockade (GI=level I; GII= level III, GIII and GIV=level II; p<0.05; GII> GI, GIII and GIV; GIII and GIV > GI). At week 24 GII, GIII and GIV evolved to a higher grade, but the difference favoring treated animals persisted. This is the first description of an experimental model of diet-induced type 2 diabetes with early features of humanoid retinopathy in rabbits. We demonstrated retinal protection by renin-angiotensin blockade. This new model can provide the opportunity for the study of target organ lesion related to diabetes, as well as for mechanistic and therapeutic studies.