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Vitamins C and E Reduce Retinal Oxidative Stress and Nitric Oxide Metabolites and Prevent Ultrastructural Alterations in Porcine Hypercholesterolemia

¹From the Department of Ophthalmology, University Clinic, and the ²Atherosclerosis Research Laboratory, Division of Cardiovascular Pathophysiology, Foundation for Applied Medical Research (FIMA), School of Medicine, University of Navarra, Pamplona, Spain.

PURPOSE. Oxidative stress is thought to be involved in the pathogenesis of age-related diseases, such as atherosclerosis and retinal degeneration. The current study was conducted to examine vitreoretinal oxidative status in a model of porcine hypercholesterolemia to identify morphologic alterations and analyze the effect of dietary supplementation with vitamins C and E.

METHODS. Adult miniature pigs were fed standard chow, cholesterol-rich chow, or a cholesterol-rich diet supplemented with vitamins C and E. Total cholesterol, triglycerides, high-density lipoproteins, lipid peroxidation, and tocopherol were measured in plasma. Lipid peroxidation and nitric oxide (NO) metabolites were measured in vitreous and retinal homogenates. Superoxide anion release in the retinal pigment epithelium (RPE) was analyzed by chemiluminescence. Retinal morphology was studied by transmission electron microscopy.

RESULTS. The high-cholesterol group, with increased retinal oxidative stress (P < 0.01) and NO metabolites in the retina (P < 0.05), had increased superoxide anion release (P < 0.05) and showed development of pyknosis, irregular nuclear membranes, and cytoplasmic accumulation of lipids and autophagocytic vacuoles in the RPE cells. Vitamins C and E prevented biochemical changes and most ultrastructural alterations in the RPE.

CONCLUSIONS. The results suggest an evolving role for hypercholesterolemia through increased retinal oxidative stress and NO synthesis that could be responsible for retinal ultrastructural alterations. The beneficial effects of vitamins C and E in the retinal tissue further support this hypothesis.

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