Omega-3 fatty acids protect retinal neurons in the DBA/2J hereditary glaucoma mouse model. (February 2018)

• Record Type: Journal Article
• Authors: Kalogerou, Maria; Kolovos, Panagiotis; Prokopiou, Ekatherine; Papagregoriou, Gregory; Deltas, Constantinos; Malas, Stavros; Georgiou, Tassos
• Is Part Of: Experimental eye research. Volume 167(2018)
• Page Start: 128
• Page End: 139
• Publication Date: 2018-02
• Subjects: DBA/2J -- Glaucoma -- Inflammation -- Neuroprotection -- Omega-3 -- Eicosapentaenoic acid -- Retinal ganglion cell; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2017.12.005
• Languages: English
• ISSNs: 0014-4835

Abstract

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/mm 2 ), ω3-PUFAs only (768.40 ± 52.44/mm 2 ) and timolol only (910.57 ± 57.28/mm 2 ) groups than in the untreated group (323.39 ± 95.18/mm 2 ). 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-α (TNF-α). 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-α may not be the only factors involved in ω3-PUFA-mediated neuroprotection in the retina. Highlights: Omega-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-α 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.