Omega-3 Fatty Acids Supplementation: Therapeutic Potential In A Mouse Model Of Stargardt Disease

PURPOSE. To evaluate the therapeutic effects of omega-3 (omega 3) fatty acids on retinal degeneration in the ABCA4(-/-) model of Stargardt disease when the blood level of arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio is between 1 and 1.5.METHODS. Eight-month-old mice were allocated to three groups: wild type (129S1), ABCA4 untreated, and ABCA4(-/-) omega 3 treated. omega 3 treatment lasted 3 months and comprised daily gavage administration of EPA and docosahexaenoic acid (DHA). Blood and retinal fatty acid analysis was performed using gas chromatography to adjust the blood AA/EPA similar to 1 to 1.5. Eyecups were histologically examined using transmission electron microscopy and confocal microscopy to evaluate lipoluscin granules and the photoreceptor layer. Retinal Nretinylidene-N-retinylethanolamine (A2E), a major component of retinal pigment epithelium lipofuscin, was quantified using liquid chromatography and tandem mass spectrometry, in addition to retinal proteomic analysis to determine changes in inflammatory proteins.RESULTS. EPA levels increased and AA levels decreased in the blood and retinas of the treatment group. Significantly less A2E and lipofuscin granules were observed in the treatment group. The thickness of the outer nuclear layer was significantly greater in the treatment group (75.66 +/- 4.80 mu m) than in the wild-type (61.40 +/- 1.84 mu m) or untreated ABCA(-/-) (56.50 +/- 3.24 mu m) groups. Proteomic analysis indicated lower levels of complement component 3 (C3) in the treatment group, indicative of lower complement. induced inflammatory response.CONCIUSIONS. Three months of omega 3 supplementation (AA/EPA, similar to 1-1.5) reduces A2E levels, lipofuscin granules, and C3 levels in the ABCA4(-/-) mouse model of Stargardt disease, consistent with slowing of the disease.