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Ryoji Yanai, Lama Mulki, Eiichi Hasegawa, Kimio Takeuhi, Harry Sweigard, Jun Suzuki, Demetrios G Vavvas, Koh-hei Sonoda, Joan W Miller, Kip M Connor; Dietary supplementation of ω-3 long chain polyunsaturated fatty acids promote choroidal neovessel resolution. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1262.
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© ARVO (1962-2015); The Authors (2016-present)
AMD is the primary cause of blindness in elderly individuals of industrialized countries. Clinical studies have indicated that dietary intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) may have a protective effect against AMD. This study characterizes the effects of dietary intake of ω-3 and ω-6 LCPUFAs in a mouse model of AMD.
The present studies adhered to ARVO’s Statement for the Use of Animals in Ophthalmic and Vision Research. C57BL/6 mice were fed a diet enriched with either ω-3 or ω-6 LCPUFAs for 2 weeks prior to choroidal neovascularization (CNV) induction by photocoagulation using a 532-nm laser. CNV development was evaluated by FA, SD-OCT, and choroidal flatmount (CFM). The primary eicosanoids and their downstream metabolites were analyzed by LC MS/MS lipidomics. Expression of ICAM-1, E-selectin, and VEGF in the retina, choroid, or laser-captured CNV were evaluated by RTPCR and immunoblot analysis. Macrophage invasion was evaluated in Cx3cr1GFP/+ mice. Leukocyte rolling velocity was analyzed using the autoperfused microflow chamber assay.
Both OCT and CFM revealed the CNV size was significantly reduced, and FA grading showed significantly less leakage in the ω-3-fed-mice compared with the ω-6-fed mice. The concentrations of the principal ω-3 LCPUFAs (EPA and DHA) were significantly increased and the AA-derived eicosanoids were significantly reduced in the serum of ω-3-fed mice. Additionally the serum levels of EPA-derived and DHA-derived CYP450 eicosanoids were significantly increased in ω-3-fed mice. The mRNA expression and abundance of protein of ICAM-1 and E-selectin in the retina or choroid after CNV induction were significantly reduced in ω-3-fed mice. The rolling velocity of leucocytes in chambers coated with P-selectin and ICAM-1 was significantly greater in ω-3-fed mice. The abundance of VEGF protein in both the retina and choroid was significantly reduced in ω-3-fed mice.
We demonstrate that dietary supplementation with ω-3 LCPUFAs mediates choroidal neovessel regression. A clear understanding of the mechanisms of these molecules in AMD could bring a major shift in our approach to disease treatment. There is an unmet need for safe nutritional or pharmacological interventions for the treatment and ideally the prevention of AMD.
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