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M.M. Campos, R.N. Fariss, M.L. Katz, W.G. Robison, Jr.; Lipofuscin Accumulation and Retinal Microangiopathies Associated with Diabetes and the Oxidative Stress of Vitamin E Deficiency . Invest. Ophthalmol. Vis. Sci. 2003;44(13):455.
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Purpose: The accumulation of lipofuscin granules has been considered to be an indicator of the cumulative oxidative stress experienced by certain tissues. It has been proposed that diabetic complications result in part from oxidative stress. In this study, lipofuscin accumulation in retinal capillaries of diabetic humans and several animal models of diabetic retinopathy was compared with that of vitamin E deficient rats that have significant oxidative tissue damage. Methods: Human eyes were obtained from diabetic donors. Vitamin E deficiency was produced by feeding rats vitamin E-free (– E) diets from weaning. Streptozotocin diabetes (STZ) was produced by intravenous injection of rats (200 g) with streptozotocin (45 mg/kg). BioBreeding Wistar (BBW) rats with inherited diabetes were maintained by daily doses of insulin. Corpulent SHR/N-cp (COR) rats were maintained without insulin. Rats were euthanized after durations of 7 to 8 and 12 to 14 months for both vitamin E deficient and diabetic groups. Retinal sections, whole mounts, and digests were examined by transmission light and electron microscopy and by epifluorescence and laser confocal microscopy using excitation and emission wave lengths specific for the autofluorescence of lipofuscin. Results: The mean non-fasting plasma glucose levels in the diabetic rat groups were as follows: STZ = 647; BBW = 385; COR = 346. In retinas of human diabetics and rat models, cell lesions were expressed as pericyte loss, endothelial cell proliferation, capillary dilations, and microaneurysms. Lipofuscin granules were found occasionally in both endothelial cells and pericytes in numbers not significantly different from controls. In the – E rats, cell damage was expressed by disruption of rod outer segments (ROS) accompanied by marked accumulation of lipofuscin pigment in retinal capillaries and the retinal pigment epithelium (RPE). The amount of lipofuscin in the retinal capillaries was many fold greater than in any other group. The retinal vessel lesions characteristic of diabetic retinopathy did not develop in – E rats. Conclusions: ROS damage and accumulation of lipofuscin in the RPE and retinal capillaries are probably good indicators of cell damage due to cumulative oxidative stress. Since ROS structure and lipofuscin accumulation remained normal in diabetes, and diabetic microangiopathies did not occur in vitamin E deficient rats, it is unlikely that oxidative stress plays a substantial role in the development of diabetic retinopathy.
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