DIETS ENRICHED IN DOCOSAHEXAENOIC ACID FAIL TO CORRECT PROGRESSIVE ROD-CONE DEGENERATION (PRCD) PHENOTYPE

Purpose. Results of a previous study show abnormal plasma lipids in pr ogressive rod-cone degeneration (prcd)-affected does, with lower docos ahexaenoic acid (DHA; 22:6n-3) and cholesterol levels but no differenc es in other plasma fatty acids, lipids, triglycerides, and fat-soluble vitamins. There is also an increase of the DHA precursor 22:5n-3, so that the ratio of 22:5n-3 to 22:6n-3 is higher in affected than in nor mal dogs. Because DHA is the predominant esterified fatty acid in rod outer segment (ROS) phospholipids, these findings suggest a possible c ausal association between abnormal plasma lipid levels and retinal deg eneration. In the current study, dietary supplements rich in 22:6n-3 w ere used to determine whether plasma, liver, and rod outer segment pho spholipid composition can be altered to mollify the prcd disease pheno type. Methods. prcd-affected and normal control dogs were given DHA-en riched supplements for short (7- and 25-day) and long (21-week) period s, and the fatty acid composition of plasma, liver, and rod outer segm ent phospholipids were examined. In the long-term study, electroretino graphy and morphology were used to assess modification of the retinal degeneration phenotype. Results. Administration of DHA-enriched supple ments resulted in increases in plasma DHA and n-3 polyunsaturated fatt y acids and in decreases in some n-6 fatty acids in normal and prcd-af fected dogs. Similar increases in DHA and n-3 fatty acids were observe d in the liver, but affected dogs had significantly higher levels at a ll supplementation time points examined. In contrast, the ROS of affec ted dogs had statistically lower (approximately 20%) DHA levels, and t hese levels could not be increased with dietary supplementation. The d isease phenotype could not be modified by DHA-enriched supplements. Co nclusions. Regardless of the sustained three- to fourfold elevation in plasma and liver DHA that occurs as the result of supplementation, th e ROS DHA levels remain unchanged, and the prcd disease phenotype is n ot modified by the dietary manipulation. These findings could be the r esult of a reduction in the synthesis of DHA-containing phospholipids in the retinas of affected dogs; or, alternatively, there could be a r eduction in DHA uptake, transport, or storage within the retinal pigme nt epithelium-photoreceptor complex.