The metabolism of omega-3 polyunsaturated fatty acids in the eye: the possible role of docosahexaenoic acid and docosanoids in retinal physiology and ocular pathology.

Study of the metabolism, physiological importance, biological effects, and pathological role of omega-3-polyunsaturated fatty acids, particularly DHA, remains a relatively unexplored field. The notion that DHA in membranes such as those of photoreceptors has no function but to contribute to membrane fluidity is probably an oversimplification. More specific roles are envisaged in the structure and function of retinal and synaptic membranes. One such function may be to provide EPA by retroconversion which, in turn, will be oxygenated to biologically active metabolites that may affect other eicosanoids or directly elicit or induce other functions. A better understanding of the already described alterations in membrane properties of outer segments in inherited retinal degeneration may also lead to further elucidation of the fundamental mechanisms involved in senile macular degeneration and other retinal diseases. The fact that aging enhances the oxidative stress on cells and that the visual cells are enriched in DHA may result in functional impairments; DHA peroxidation may deplete crucial phospholipids from their sites in specific membrane domains. Also, DHA peroxidation generates toxic products that can damage the shedding of photoreceptor discs or their phagocytosis by the retinal pigment epithelium. Docosanoids, oxygenated derivatives of DHA that resemble eicosanoids, may well prove to be unique mediators of physiological processes in the central nervous system, including the retina, and may play a role in some ocular pathologies. More thorough knowledge of these compounds can be expected to lead to important new insights into ocular physiology and pathophysiology, just as research on the eicosanoid system, the primary subject of this volume, has achieved. However, it is of even more immediate importance that we bear in mind the potential contribution of docosanoids to retinal physiology and pathology and to other ocular processes when considering treatment modalities or when interpreting the results of research studies that involve manipulation of the cyclooxygenase and lipoxygenase pathways. The effects currently assigned to eicosanoids by virtue of their inhibition of the cyclooxygenase or lipoxygenase systems may, in part, be consequences of concomitant alterations in the production of docosanoids, especially in the eye, where the retina is an especially rich source of DHA, the endogenous precursor of this recently discovered family of metabolites.