Objective To evaluate the therapeutic effects of omega-3 (ω3) fatty acids in the retina of aged mice when the blood arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio is maintained between 1.0 and 1.5.
Methods and analysis Aged (24-month-old) wild-type C57BL/6J mice were allocated to two groups: ω3 treated and untreated. Treatment with ω3 was by daily gavage administration of EPA and docosahexaenoic acid for 60 days. Gas chromatography was used to identify and quantify fatty acids in the blood and retina. To count lipofuscin granules and measure the photoreceptor layer, eyecups were examined histologically using transmission electron microscopy and light microscopy. We also analysed eyecups using mass spectrometry-based proteomics.
Results AA levels were lower, and EPA levels were higher, in the blood and retinas of the ω3-treated group than in the untreated group, resulting in a lower AA/EPA ratio. The ω3-treated group also showed significantly fewer lipofuscin granules and a thicker outer nuclear layer than the untreated group. Proteomic analysis revealed significantly greater expression of myelin basic protein, myelin regulatory factor-like protein, myelin proteolipid protein and glial fibrillar acidic protein in the ω3-treated group than in the untreated group. Three different pathways were significantly affected by ω3 treatment: fatty acid elongation, biosynthesis of unsaturated fatty acids and metabolic pathways.
Conclusion Two months of ω3 supplementation (when the blood AA/EPA~1.0–1.5) in aged mice reduced lipofuscin granule formation in the retina and protected the photoreceptor layer, suggesting that ω3 supplementation slows normal age-related retinal degeneration.
- experimental and animal models
- treatment other
- experimental & laboratory
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Contributors EP and PK designed and performed the experiments. MK, LP, CG and KS contributed to some of the experimental procedures. TG supplied the reagents/materials/analysis tools. TG and KK provided guidance and support. EP analysed the data and wrote the manuscript. All contributing authors have read and approved the ﬁnal version of the manuscript.
Funding This research was supported by Ophthalmos Research and Educational Institute (Nicosia, Cyprus) and was not supported by any speciﬁc grant from funding agencies in the public, commercial, or not-for-proﬁt sectors.
Competing interests TG has a patent on the use of omega-3 fatty acids in eye diseases.
Patient consent for publication Not required.
Ethics approval The animal care and experimental procedures were performed in accordance with the EU Directive 2010/63/EU for animal experiments and approved by the Cyprus Government’s Chief Veterinary Officer.
Provenance and peer review Not commissioned; externally peer reviewed.
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