Dietary Omega-3 Fatty Acids Suppress Experimental Autoimmune Uveitis in Association with Inhibition of Th1 and Th17 Cell Function

Abstract

Omega (ω)–3 long-chain polyunsaturated fatty acids (LCPUFAs) inhibit the production of inflammatory mediators and thereby contribute to the regulation of inflammation. Experimental autoimmune uveitis (EAU) is a well-established animal model of autoimmune retinal inflammation. To investigate the potential effects of dietary intake of ω-3 LCPUFAs on uveitis, we examined the anti-inflammatory properties of these molecules in comparison with ω-6 LCPUFAs in a mouse EAU model. C57BL/6 mice were fed a diet containing ω-3 LCPUFAs or ω-6 LCPUFAs for 2 weeks before as well as after the induction of EAU by subcutaneous injection of a fragment of human interphotoreceptor retinoid-binding protein emulsified with complete Freund’s adjuvant. Both clinical and histological scores for uveitis were smaller for mice fed ω-3 LCPUFAs than for those fed ω-6 LCPUFAs. The concentrations of the T helper 1 (Th1) cytokine interferon-γ and the Th17 cytokine interleukin-17 in intraocular fluid as well as the production of these cytokines by lymph node cells were reduced for mice fed ω-3 LCPUFAs. Furthermore, the amounts of mRNAs for the Th1- and Th17-related transcription factors T-bet and RORγt, respectively, were reduced both in the retina and in lymph node cells of mice fed ω-3 LCPUFAs. Our results thus show that a diet enriched in ω-3 LCPUFAs suppressed uveitis in mice in association with inhibition of Th1 and Th17 cell function.

Dietary Factors Associated with Plasma Thyroid Peroxidase and Thyroglobulin Antibodies

“…Studies performed in experimental animals showed that a diet enriched with n -3 fatty acids suppresses the inflammation that accompanies autoimmune reactions [ 18 , 19 , 20 , 21 ]. The results indicate that n -3 PUFAs reduce the differentiation of Th17 cells from naive CD4+ T cells by modifying the lipid rafts regions in their plasma membrane and decreasing the formation of IL-6 receptors [ 18 ].…”

Oral Omega-3 Supplementation Lowers Intraocular Pressure in Normotensive Adults

“… 6 Omega-3 supplementation can modify the expression of tear inflammatory cytokines in dry eye patients 17 and suppress retinal inflammation in experimental models of autoimmune uveitis. 20 Therefore, systemic anti-inflammatory modulation may contribute to the observed IOP-lowering effects, possibly through effects on outflow resistance through the trabecular meshwork and/or modulation of uveoscleral outflow; further investigation is required to explore these hypotheses.…”

Attenuation of choroidal neovascularization by dietary intake of ω-3 long-chain polyunsaturated fatty acids and lutein in mice

“…Dietary enrichment with ω-3 LCPUFAs such as DHA and EPA present in fish oil and certain plant and nut oils [ 2 , 20 , 21 ] has been shown to protect against inflammation [ 22 , 23 ], pathological angiogenesis [ 24 ], and tumorigenesis [ 25 – 31 ]. We have previously shown that leukocyte recruitment to and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs, and that 17,18-epoxyeicosatetraenoic acid (EEQ) and 19,20-epoxydocosapentaenoic acid (EDP), the major metabolites of ω-3 LCPUFAs generated by cytochrome P450, were key mediators of disease resolution [ 18 ]. We have now shown that dietary ω-3 LCPUFAs reduced the level of oxidative stress in the retina of AMD model mice likely through down-regulation of Nox4 expression.…”

“…The mice were assigned to four groups: (1) a control group fed an ω-3 LCPUFA–free diet, (2) a lutein group fed an ω-3 LCPUFA–free diet with oral administration of lutein, (3) an ω-3 group fed an ω-3 LCPUFA–supplemented diet, and (4) an ω-3 + lutein group fed an ω-3 LCPUFA–supplemented diet with oral administration of lutein. The animals were thus transferred to a diet that was either supplemented with or free of ω-3 LCPUFAs ( Fig 1 ), as described previously [ 18 ] (Oriental Yeast, Tokyo, Japan). In addition, mice received 0.055 ml (0.5 mg/kg) of lutein (Koyojapan, Tokyo, Japan) or vehicle (control and ω-3 groups) via an oral gavage needle daily beginning 1 week after the onset of feeding with either defined diet.…”

“…Forty mice of each group were subjected to laser photocoagulation in both eyes at 2 weeks after the onset of feeding with the defined diets. The procedure was performed as described previously [ 18 ] with settings including a spot size of 75 μm, pulse duration of 0.1 s, and laser power of 200 mW. One investigator (S.C.) executed all laser photocoagulation.…”