Docosahexaenoic acid (DHA, 22:6n-3) is a long-chain, highly polyunsaturated n-3 fatty acid. It accounts for about 5O percent of the fatty acids within photoreceptor outer segment disk membranes, the site of phototransduction. Retinal function is altered by changes in retinal membrane DHA content. Rhesus monkeys fed low levels of n-3 fatty acids during development had reduced retinal DHA, impaired visual acuity development and several changes in the electroretinogram (ERG), including prolonged recovery of isolated rod photoreceptor responses to bright, a-wave-saturating flashes. Human infants fed formulas lacking DHA, or containing low levels of its precursors, also showed impairments in the ERG and visual acuity development. In addition, low DHA levels are found in the blood and tissues of many human patients with retinitis pigmentosa and in animal models of retinal degeneration, and dietary DHA is being tested as a possible therapeutic treatment. Despite these indications of DHAs importance in the retina, the nature of the changes in retinal function associated with altered fatty acid composition have not been explored in detail and little is known about their underlying mechanisms. We plan to examine several aspects of retinal function in rhesus monkeys raised on diets with different levels of n-3 fatty acids known to result in widely differing retinal DHA levels. A series of recently developed non-invasive ERG methods will allow us to define effects on phototransduction and photoresponse recovery as well as on rhodopsin regeneration.
Specific aims i nclude testing the effects of DHA status on: (1) the activation and deactivation kinetics of isolated rod photoresponses over a wide range of flash intensities; (2) the desensitization of rod responses by background light; and (3) the time-course of dark adaptation over a range of bleaches. In addition, aim 4 will be to test whether any of these alterations in photoreceptor function are reversible after dietary DHA repletion. These studies will provide new information about the modification of retinal function, particularly adaptive processes, by membrane DHA content. Together with in vitro studies of model membranes, these data will help to provide the basis for hypotheses about the underlying processes that are altered by differing retinal fatty acid compositions. They also will contribute to understanding the changes in retinal function found in human infants fed diets lacking DHA or its precursors.
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