LAUSR

Abstract The purpose of this study was to evaluate the neuroprotective effects of omega‐3 polyunsaturated fatty acid (ω3‐PUFA) supplementation, alone or in combination with timolol eye drops, in a mouse model of hereditary glaucoma. DBA/2J mice (8.5‐month‐old) were assigned to an ω3‐PUFAs + timolol, ω3‐PUFAs only, timolol only, or an untreated group. Treated mice received a daily gavage administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid and/or topical instillation of timolol (0.5%) once a day for 3 months. Blood was analysed regularly to determine ω3‐PUFA levels and retinas were histologically analysed. Real‐time PCR and Western blot were performed for retinal pro‐inflammatory cytokines and macrophages. Blood arachidonic acid/EPA ratio gradually decreased and reached the desired therapeutic range (1–1.5) after 4 weeks of daily gavage with ω3‐PUFAs in the ω3‐PUFAs + timolol and ω3‐PUFAs only groups. Retinal ganglion cell densities were significantly higher in the ω3‐PUFAs + timolol (1303.77 ± 139.62/mm2), ω3‐PUFAs only (768.40 ± 52.44/mm2) and timolol only (910.57 ± 57.28/mm2) groups than in the untreated group (323.39 ± 95.18/mm2). ω3‐PUFA supplementation alone or timolol alone, significantly increased protein expression levels of M1 macrophage‐secreted inducible nitric oxide synthase and M2 macrophage‐secreted arginase‐1 in the retina, which led to significant decreases in the expression levels of tumour necrosis factor‐&agr; (TNF‐&agr;). ω3‐PUFA supplementation alone also resulted in significantly reduced expression of interleukin‐18 (IL‐18). ω3‐PUFA + timolol treatment had no effect on the expression level of any of the aforementioned mediators in the retina. Supplementation with ω3‐PUFAs has neuroprotective effect in the retinas of DBA/2J mice that is enhanced when combined with timolol eye drops. The continued inflammation following ω3‐PUFAs + timolol treatment suggests that downregulation of IL‐18 and TNF‐&agr; may not be the only factors involved in ω3‐PUFA‐mediated neuroprotection in the retina. HighlightsOmega‐3 PUFA treatment has neuroprotective effect in retinas of DBA/2J mice that is enhanced when combined with timolol.Downregulation of IL‐18 and TNF‐&agr; may not be the only factor involved in ω3‐PUFA‐mediated neuroprotection in the retina.These novel data might indicate a turning point in the current treatment approach for patients with glaucoma.