Exogenous advanced glycosylation end products induce diabetes-like vascular dysfunction in normal rats: a factor in diabetic retinopathy

BACKGROUND. Diabetic retinopathy has been shown to be directly associated with the degree and duration of hyperglycemia, and advanced glycosylation end products (AGEs) have been implicated in this pathological process. The purpose of the experiments reported here was to study the effect of AGE deposition on retinal vascular damage which leads to diabetic retinopathy. METHODS. Intravenous injection of exogenous AGEs was used to treat wild-type non-diabetic Sprague-Dawley rats. One of the two retinal slides from each animal was treated using immunohistochemical staining to label retinal vascular AGE deposition, the other H&E staining for counting of capillary pericytes. The results were compared with the findings in untreated wild-type and diabetic controls and in rats treated with unmodified rat serum albumin (RSA). RESULTS. After 2 weeks of continuous treatment, AGEs were identified in the retinal vascular tissue of the AGE-RSA-injected group. The average number of retinal capillary pericytes per 10x100 microscope power field was 4.313+/-0.34 (mean +/- SD) in the AGE-RSA-injected group, compared with 5.798+/-0.481 in the control group ( P<0.01). CONCLUSION. These experiments demonstrate that AGEs, independent of other metabolic factors, can induce vascular change resembling that of diabetic retinopathy.