Diets enriched in docosahexaenoic acid fail to correct progressive rod-cone degeneration (prcd) phenotype

Abstract

Purpose: Results of a previous study show abnormal plasma lipids in progressive rod-cone degeneration (prcd)-affected dogs, with lower docosahexaenoic acid (DHA; 22:6n-3) and cholesterol levels but no differences 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 normal dogs. Because DHA is the predominant esterified fatty acid in rod outer segment (ROS) phospholipids, these findings suggest a possible causal association between abnormal plasma lipid levels and retinal degeneration. In the current study, dietary supplements rich in 22:6n-3 were used to determine whether plasma, liver, and rod outer segment phospholipid composition can be altered to modify the prcd disease phenotype.

Methods: prcd-affected and normal control dogs were given DHA-enriched supplements for short (7- and 25-day) and long (21-week) periods, and the fatty acid composition of plasma, liver, and rod outer segment phospholipids were examined. In the long-term study, electroretinography and morphology were used to assess modification of the retinal degeneration phenotype.

Results: Administration of DHA-enriched supplements resulted in increases in plasma DHA and n-3 polyunsaturated fatty acids and in decreases in some n-6 fatty acids in normal and prcd-affected dogs. Similar increases in DHA and n-3 fatty acids were observed in the liver, but affected dogs had significantly higher levels at all supplementation time points examined. In contrast, the ROS of affected dogs had statistically lower (approximately 20%) DHA levels, and these levels could not be increased with dietary supplementation. The disease phenotype could not be modified by DHA-enriched supplements.

Conclusions: Regardless of the sustained three- to fourfold elevation in plasma and liver DHA that occurs as the result of supplementation, the ROS DHA levels remain unchanged, and the prcd disease phenotype is not modified by the dietary manipulation. These findings could be the result of a reduction in the synthesis of DHA-containing phospholipids in the retinas of affected dogs; or, alternatively, there could be a reduction in DHA uptake, transport, or storage within the retinal pigment epithelium-photoreceptor complex.