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

Dietary omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) and lutein each protect against age-related macular degeneration (AMD). We here examined the effects of omega-3 LCPUFAs and lutein supplementation in a mouse model of AMD. Mice were assigned to four groups: (1) a control group fed an omega-3 LCPUFA +/- free diet, (2) a lutein group fed an omega-3 LCPUFA +/- free diet with oral administration of lutein, (3) an omega-3 group fed an omega-3 LCPUFA +/- supplemented diet, and (4) an omega-3 + lutein group fed an omega-3 LCPUFA +/- supplemented diet with oral administration of lutein. Mice were fed the defined diets beginning 2 weeks before, and received lutein with an oral gavage needle beginning 1 week before, induction of choroidal neovascularization (CNV) by laser photocoagulation. The area of CNV measured in choroidal flat-mount preparations was significantly reduced in mice fed omega-3 LCPUFAs or lutein compared with those in the control group, and it was reduced in an additive manner in those receiving both omega-3 LCPUFAs and lutein. The concentrations of various inflammatory mediators in the retina or choroid were reduced in mice fed omega-3 LCPUFAs or lutein, but no additive effect was apparent. The generation of reactive oxygen species (ROS) in chorioretinal lesions revealed by dihydroethidium staining as well as the expression of NADPH oxidase 4 (Nox4) in the retina revealed by immunohistofluorescence and immunoblot analyses were attenuated by omega-3 LCPUFAs and lutein in a synergistic manner. Our results thus show that dietary intake of omega-3 LCPUFAs and lutein attenuated CNV in an additive manner and in association with suppression of inflammatory mediator production, ROS generation, and Nox4 expression. Dietary supplementation with both omega-3 LCPUFAs and lutein warrants further study as a means to protect against AMD.