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

Abstract

Dietary ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) and lutein each protect against age-related macular degeneration (AMD). We here examined the effects of ω-3 LCPUFAs and lutein supplementation in a mouse model of AMD. 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. 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 ω-3 LCPUFAs or lutein compared with those in the control group, and it was reduced in an additive manner in those receiving both ω-3 LCPUFAs and lutein. The concentrations of various inflammatory mediators in the retina or choroid were reduced in mice fed ω-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 ω-3 LCPUFAs and lutein in a synergistic manner. Our results thus show that dietary intake of ω-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 ω-3 LCPUFAs and lutein warrants further study as a means to protect against AMD.

Effects of lutein supplementation in age-related macular degeneration

“…Lutein protects the retina by filtering out blue light and acting as an antioxidant [2, 41], and administering it to animals can significantly increase anti-oxidant enzyme levels and total anti-oxidant capacity [42]. Lutein and other carotenoids also suppress production of inflammatory mediators and reactive oxygen species, and they down-regulate NADPH oxidase subunit Nox4 [43, 44]. In cell culture studies, lutein protected ARPE-19 retinal cells from oxidative stress-induced cellular senescence [45], likely by quenching singlet oxygen [46].…”

Nutraceuticals for the Treatment of Diabetic Retinopathy

“…Dietary lutein has been shown recently to promote a decrease in the extent of CNV induced by laser photocoagulation in mice. This effect increases in an additive manner when lutein is administered together with ω-3 long-chain polyunsaturated fatty acids and it is accompanied by reductions in oxidative stress and in inflammatory mediators [182].…”

Update on the Effects of Antioxidants on Diabetic Retinopathy: In Vitro Experiments, Animal Studies and Clinical Trials

“…Recently, it was found that this beneficial effect on the retina can be increased synergistically when lutein is administered in association with Ω-3 long-chain polyunsaturated fatty acids. An antioxidant and anti-inflammatory effect were found by reducing ROS production and inhibiting the expression of inflammatory mediators [ 21 ]. In this sense, the fish oil emulsion, rich in Ω-3 polyunsaturated fatty acids, has anti-inflammatory and antioxidant in vitro properties, with the capability to inhibit the production of pro-inflammatory growth factors and cytokines [ 22 ].…”