13-hydroperoxylinolenic-acid and Retinal-Degeneration

Lipid hydroperoxides (LHP) have been synthesized and purified from linoleic, linolenic, arachidonic and docosahexaenoic acids, using soybean lipoxygenase and oxygen. Intravitreal injections into the eyes of mature, albino rabbits produced an early and then progressive decrease in the amplitude of a-, b- and c-waves of the ERG. Depending upon the amount and activity of the LHP preparation, ERG's were markedly decreased in amplitude (greater than 50%) within 4 days following the injection and by 12 days, the activity from peroxide treated eyes was essentially nonrecordable. In preliminary studies, these effects were less pronounced in adult pigmented rabbits of similar age, however, a younger pigmented rabbit was only slightly less susceptible to damage than the albino animals. In other experiments, peroxidized native phospholipids, malonaldehyde, hydrogen peroxide and sodium iodate were also shown to be cytotoxic, but not all were as toxic as the LHP. In contrast, retinol, vitamin A acetate and retinoic acid had no effect upon ERG activity, nor did the parent fatty-acid compounds or the borate buffer in which they were injected. These studies confirm previous reports where indirect production of lipid peroxides caused retinal degeneration. The present report extends these observations to demonstrate that when the retina and RPE are exposed to a sample of purified LHP, retinal function is altered in an irreversible way. We also demonstrate that a metabolic by-product (malonaldehyde) is likewise cytotoxic. However, the mechanisms by which the parent LHP and/or metabolites might act could be quite different. This new animal model should prove useful in evaluating further the ultrastructural changes which are observed during peroxidative damage of the retina in vivo, as well as in evaluating the therapeutic approaches to these problems of retinal degeneration.

Topics: Animals; Arachidonic Acids; Diterpenes; Docosahexaenoic Acids; Electroretinography; Leukotrienes; Linolenic Acids; Lipid Peroxides; Rabbits; Retina; Retinal Degeneration; Retinyl Esters; Vitamin A