Omega‐3 fatty acids supplementation: therapeutic potential in a mouse model of Stargardt's disease

Abstract

PurposeTo evaluate the therapeutic effects of omega‐3 (ω‐3) fatty acids in the ABCA4‐/‐ model of Stargardt's disease. Monitoring the blood level of eicosapentaenoic acid (EPA) and arachidonic acid (AA), served to adjust the treatment dosage (AA/EPA = 1‐1.5).MethodsEight‐month‐old mice were allocated to different groups: A) wild type (129S1), B) ABCA4‐/‐ untreated, C) ABCA4‐/‐ treated with ω‐3. Treatment was daily administered by gavage for 3 months. Eye cups from each group were histologically examined using confocal and transmission electron microscopy. Proteomic analysis and N‐retinylidene‐N‐retinylethanolamine (A2E) quantification was carried our using liquid chromatography mass spectrometry (LC‐MS/MS). Blood and retinal fatty acids analysis was performed using gas chromatography (GC).ResultsA significant decrease in melanolipofuscin granules in the retinal pigment epithelium (RPE) was observed in the treatment group, in parallel with a reduction in A2E level, a major component of RPE lipofuscin. Proteomic analysis indicated decreased levels of complement 3 (C3) in the treated group. The outer nuclear layer (ONL) thickness was significantly greater in group C (75.66 ± 4.8 μm), compared to group A (61.40 ± 1.84 μm) and B (56.50 ± 3.24 μm). Increased EPA and decreased AA levels were observed in both blood and retinas in the treatment group.ConclusionsSupplementation with ω‐3 fatty acids (when AA/EPA = 1‐1.5) suggests a protective mechanism in the ABCA4‐/‐ animal model of Stargadt's disease.