Retinal vascular changes induced by the oxidative stress of alpha-tocopherol deficiency contrasted with diabetic microangiopathy

It has been proposed that oxidative tissue damage is involved in the develo pment of diabetic angiopathies. To evaluate this hypothesis, experiments we re conducted to identify the retinal vessel changes induced by the oxidativ e stress related to alpha-tocopherol deficiency and examine possible simila rities with the lesions characteristic of diabetic retinopathy. Twenty-one- day-old male Fisher 344 albino rats were divided randomly to receive a basa l, chemically defined diet either with (adequate group) or without (deficie nt group) alpha-tocopherol. After 6 and 8 months, some rats (n = 3 per grou p) were killed and the eves removed. In order to evaluate cell integrity an d localization of lipofuscin-specific autofluorescence by light and fluores cence microscopy, some of the retinas were prepared for cryostat-sections w hile others were digested by elastase to isolate intact retinal vasculature s. After 8 and 14 months, the central retina of one eye per rat (n = 6 to 8 per group) was examined by electron microscopy for retinal capillary basem ent membrane (RCBM) thickening and other ultrastructural changes. At 6 and 8 months, the deficient rats exhibited extensive shortening and disarray of rod outer segments (ROS), marked loss of photoreceptor cells, and pronounc ed increases in the numbers of granules with lipofuscin-specific autofluore scence in the retinal pigment epithelium (RPE) and retinal vessels. At 14 m onths, the ultrastructure revealed that the damage to ROS involved disrupti on of membranes and that the capillary lipofuscin was contained mainly with in the endothelial cells. Membrane remnants were found in the lipofuscin gr anules of both the RPE and retinal vessels. In addition, there was an incre ase in RCBM thickness (98.7 +/- 2.6 nm vs. 86.9 +/- 2.9 nm). RCBM thickenin g was the only finding common with diabetic retinopathy, and the thickening was 13.6%, significantly less than that reported in diabetic rat models wi th 8 and 14 months durations (34% and 53.1%, respectively). Capillary lipof uscin accumulation, which was prominent in the deficient rats, is not notab le in diabetes. Both the moderate RCBM thickening and marked lipofuscin acc umulations seen in alpha-tocopherol-deficient rats were similar to changes occurring in the aging process, though more pronounced. The spectrum of mic roangiopathies characteristic of diabetic retinopathy did not develop in al pha-tocopherol-deficient rats. These findings suggest that oxidative damage , though probably involved, is unlikely to play a predominant role in the d evelopment of diabetic retinal microangiopathies.