Therapeutic potential of omega-3 fatty acids supplementation in a mouse model of dry macular degeneration

Abstract

Purpose To evaluate the therapeutic effects of omega-3 (ω-3) and omega-6 (ω-6) fatty acids in the CCL2-/- model of dry age-related macular degeneration (AMD). The blood level of eicosapentaenoic acid (EPA) and arachidonic acid (AA) served to adjust the treatment dosage (AA/EPA=1-1.5). Methods Nine-month-old animals were allocated to different groups: (A) C57BL/6 untreated, (B) CCL2-/- untreated, (C) CCL2-/- treated with ω-3+ω-6, and (D) CCL2-/- treated with ω-3. Treatment was daily administered by gavage for 3 months. Fatty acids analysis was performed and retinas were histologically examined. Three-month-old wild type mice were used for comparison purposes. Real-time PCR and Western blot were performed for retinal inflammatory mediators. Results Increased EPA and decreased AA levels were observed in both blood and retinas in the treatment groups. The outer nuclear layer thickness was increased in groups C (45.0±3.9 μm) and D (62.8±4.9 μm), compared with groups B (65.6±3.0 μm) and A (71.1±4.2 μm), and in younger mice, it was 98.0±3.9 μm. A decrease in NF-κB expression was noted in the treatment groups. Interleukin (IL) 18 protein levels demonstrated a significant reduction in the ω-3-treated group only. Conclusion Supplementation with ω-3+ω-6 or ω-3 alone (AA/EPA=1-1.5) suggests a protective mechanism in the CCL2-/- animal model of dry AMD, with a more beneficial effect when ω-3 are used alone. Our findings indicated that inflammation is not the only determining factor; perhaps a regenerative process might be involved following administration of ω-3 fatty acids.