Decreasing the Dietary Intake of Linoleic Acid Promotes the Efficacy of Dietary Long Chain Omega-3 Fatty Acids to Incorporate the Rat Retina and Modifies Gene Expression

Abstract

Purpose: : Age-related Macular Degeneration (AMD) is the leading cause of blindness and visual disability in patients 60 years or older in the Western hemisphere. It may partially be prevented by dietary habits privileging the consumption of ω3 long chain polyunsaturated fatty acids (ω3s), and lowering linoleic acid (LA) intakes meanwhile. The aim of our study was to document whether following those epidemiological-based guidelines would enhance the enrichment of the neurosensory retina and RPE with ω3s, and modulate gene expression in the neurosensory retina.

Methods: : Rats were fed with diets containing low or high LA, and low or high ω3s (EPA, DPA and DHA) for one generation. The functionality of the retina adult offspring was evaluated by single flash electroretinography (ERG) under scotopic conditions to assess the global response of the retina. The a-wave was used to reflect the response of photoreceptors, and the b-wave the response of the inner layers of the retina. Flicker ERG was monitored by increasing flash intensity at 8Hz-fixed frequency of the stimulus to specifically assess the sensitivity of rods and cones. Fatty acid profile of the neurosensory retina, RPE, liver, adipose tissue and plasma was analyzed by gas chromatography. Expression of genes involved in lipid metabolism was analyzed by real-time PCR in the neurosensory retina.

Results: : Diets rich in ω3s improve the incorporation of ω3 LC-PUFAs in plasma, adipose tissue, liver, neurosensory retina and RPE. The raising effect of ω3 LC-PUFA supplementation on EPA and DPA ω3 incorporation in the neurosensory retina is magnified in rats fed with diets containing low LA. Low LA diets significantly up-regulated LDL-receptor gene expression compared to diet with high LA and low ω3s. Similar but not significant up-regulation of CD36, ABCA1, ALOX5 and ALOX12 gene expression was observed in rats fed with low LA. No effect was observed on retinal function and retinal sensitivity.

Conclusions: : Increasing the intake in ω3s and lowering LA improved the enrichment with ω3s of the tissues, including the neurosensory retina and RPE, and up-regulated genes involved in lipid trafficking in the neurosensory retina. Those results consistently reinforced the beneficial role of ω3s in the prevention of AMD, especially when the diet contained low LA, as suggested from epidemiological data.

Keywords: lipids • neuroprotection • gene/expression