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Ryoji Yanai, Lama Mulki, Kimio Takeuchi, John Sweigard, Jun Suzuki, Philipp Gaissert, Demetrios Vavvas, Wolf-Hagen Schunck, Joan Miller, Kip Connor; Omega-3 long chain polyunsaturated fatty acids promote choroidal neovessel regression. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3280.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration (AMD) is the primary cause of blindness in elderly individuals of industrialized countries. Prospective clinical studies have indicated that dietary intake of omega (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 Fluorescein Angiography (FA), Optical Coherence Tomography (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 were 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 in serum of ω-3-fed mice. The serum levels of AA-derived eicosanoids were significantly reduced, whereas those of EPA-derived- and DHA-derived 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 on the combination of P-selectin and ICAM-1 coated chamber 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 of ω-3 LCPUFAs mediate 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. Currently there is an urgent need for safe nutritional or pharmacological interventions for the treatment and ideally the prevention of AMD.
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