Effects of Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Antagonist in Diabetic Rabbit Retina

Abstract

Purpose: : 1. To verify the effects of the angiotensin converting enzyme inhibitor (ACEI) quinapril and the angiotensin II receptor antagonist (ARA) olmesartan on retina of hypercholesterolemic and diet-induced diabetic rabbits. 2. To present a new animal model for diabetic retinopathy in rabbit eyes.

Methods: : Diabetes and hypercholesterolemia were induced in New Zealand white male rabbits by a diabetogenic and cholesterol-rich diet with high-fat/high-sucrose diet, maintained for 6 months. After 12 and 24 week period, the efficacy of diet to inducing diabetes and hypercholesterolemia was examined by plasma glucose levels, total cholesterol, high-density lipoprotein, cholesterol and triglyceride. The rabbits were divided into four groups. Groups II, III and IV received the high-fat/high-sucrose diet. Animals from group I (n=10) formed the control group, and from group II (n=10) formed the untreated group. Animals from group III (n=10) received the quinapril, and from group IV (n=10) received the olmesartan orally, added to the chow. Fundus photographs and fluorescein angiography were performed at the third and sixth month. The prevalence of retinopathy was determined based on the presence of microaneurysms on standard photographs. An area of radius equivalent to the diameter of average optic disc, within 1500 micrometers of the border of optic disc, was evaluated. The number of microaneurysms was counted and retinopathy was graduated into 4 levels on the amount of microaneurysms: I - 40.

Results: : All the animals induced by diet were diabetics at 6 months after induction (glycemia 316±127.21 mg/dl). No differences between groups II, III and IV were observed regarding glucose levels. The control group (I) had a mean glycemia of 104±5.3 mg/dl. Clinical study of all diabetic groups (II, III and IV) by 12 weeks revealed the early clinical features of diabetic retinopathy included hyperfluorescent dots consistent with microaneurysms. Group II developed microaneurysms at grade IV, while groups III and IV presented microaneurysms at grade III. Clinical findings did not change appreciably by 24 weeks and there were no differences among the groups.

Conclusions: : 1. No significant clinical benefit was observed regarding retinal protection with the use of ACEI or ARA for the treatment of diabetic retinopathy in this model. 2. New Zealand white rabbits fed with high-fat/high-sucrose diet seem to provide a convenient animal model to studying diabetic retinopathy.

Keywords: diabetic retinopathy • retina • diabetes