Gut inflammation affects retinal fatty acid composition.

Abstract

Inflammation and altered lipid metabolism - particularly bioavailability of polyunsaturated fatty acids of the omega-3 series (n-3 PUFAs) - are associated with age-related macular degeneration (AMD). Growing evidence suggests that the gut plays a significant role in regulating retinal physiology. Recent studies have reported that patients with chronic inflammatory bowel diseases (IBD) may have an increased risk of developing AMD. We investigated the influence of colitis on retinal fatty acids, by using a dextran sodium sulfate (DSS)-induced colitis model in mice. Compared to control mice, the retinas of DSS-treated mice exhibited a significantly higher amount of PUFAs, accompanied by a decrease in saturated fatty acids. Both retinal n-6 and n-3 PUFAs were affected by the DSS-induced colitis, including C20:4n-6 (arachidonic acid, the main retinal n-6 PUFA), and C22:6n-3 (docosahexaenoic acid, the main retinal n-3 PUFA), without altering their ratio. Analysis of gene expression involved in fatty acid biosynthesis revealed that, while Elovl2, Elovl4, and Elovl5 expression levels remained unchanged, Fasn expression tended to decrease and Fads2 expression was significantly reduced in the retinas of DSS-treated mice compared to those of controls. Besides, the retinal expression level of genes encoding pro-inflammatory cytokines (Il1b, Il6, Il8 and Tnfa) was not modified by the DSS-induced colitis. Altogether, these results indicate that although retinal cells do not express a pro-inflammatory phenotype, colitis influences the retinal bioavailability of fatty acids. In addition to providing new insights into the potential link between IBD and AMD, this study also supports the concept that gut health influences retinal physiology.