Omega-3 fatty acids supplementation protects the retina from age-associated degeneration in aged C57BL/6J mice

Prokopiou, Ekatherine; Kolovos, Panagiotis; Georgiou, Christos D.; Kalogerou, Maria; Potamiti, Louiza; Sokratous, Kleitos; Kyriacou, Kyriacos; Georgiou, Tassos

doi:10.1136/bmjophth-2019-000326

Cited by 24 publications

(13 citation statements)

References 66 publications

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“…Previous studies found no or marginal increases in retinal omega-3 levels even after treatment with very high concentrations of dietary omega-3 FA. For example, Prokopiou et al [ 40 ] fed aged (2-year-old) mice 200 mg omega-3 FA/day in the form of fish oil for 60 days, and found actually a decrease in retinal DHA (−21%), although retinal EPA, which is a minor constituent, increased by 42%. Similarly, gavaging ABCA4−/− mice (Stargardt disease) with 206 mg/day of omega-3 FA (172 mg EPA + 34 mg DHA) for three months resulted in no change in retinal DHA, although a 67% increase in retinal EPA (from 0.93% to 1.56% of total) was observed [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Efficient Enrichment of Retinal DHA with Dietary Lysophosphatidylcholine-DHA: Potential Application for Retinopathies

2020

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Although decreased retinal docosahexaenoic acid (DHA) is a known risk factor for retinopathy, currently available omega-3 fatty acid supplements, which are absorbed as triacylglycerol (TAG), do not significantly enrich retinal DHA. We tested the hypothesis that lysophospahtidylcholine (LPC)-DHA which is absorbed as phospholipid, would efficiently increase retinal DHA because of the presence of LPC-specific transporter at the blood–retina barrier. In normal rats, LPC-DHA and di-DHA phosphatidylcholine (PC), which generates LPC-DHA during digestion, increased retinal DHA by 101% and 45%, respectively, but TAG-DHA had no significant effect at the same dose (40 mg/kg, 30 days). In normal mice, both sn-1 DHA LPC and sn-2 DHA LPC increased retinal DHA by 80%, but free DHA had no effect. Lipase-treated krill oil (which contains LPC-DHA and LPC-EPA (eicosapentaenoic acid), but not normal krill oil (which has little LPC), increased both retinal DHA (+76%) and EPA (100-fold). Fish oil, however, had no effect, whether lipase-treated or not. These studies show that retinal DHA can be efficiently increased by dietary LPC-DHA, but not by TAG-DHA or free DHA. Since DHA is known to be protective against retinopathy and other eye diseases, this study provides a novel nutraceutical approach for the prevention/treatment of these diseases.

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Section: Discussionmentioning

confidence: 99%

Efficient Enrichment of Retinal DHA with Dietary Lysophosphatidylcholine-DHA: Potential Application for Retinopathies

2020

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“…Increasing scientific evidence highlights the crucial role of diet (48), probiotics (49) and nutraceutical (50) products on biological processes (pathogen resistance, xenobiotic and drug metabolism, delay in the aging process, prevention of chronic diseases, increase in life expectancy, or support in the structure or function of the body) and, consequently, on human health and diseases, including cancer (51)(52)(53)(54)(55).…”

Section: Discussionmentioning

confidence: 99%

The double effect of walnut septum extract (Juglans regia L.) counteracts A172 glioblastoma cell survival and bacterial growth

et al. 2020

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Walnut ( Juglans regia L.) is considered to be a 'superfood' for its multiple protective actions on human health. Walnut extracts have proven antitumor activity in different cancer cell lines. However, the efficacy of septum extract against glioblastoma has still not been investigated. Glioblastoma is the most difficult type of brain cancer to treat. The standard therapy, based on temozolomide, causes several side effects, including neutropenia and lymphocytopenia, which often favor the onset of opportunistic infections. In the present study, the chemical profile of the Sicilian walnut septum ethanolic extract was analyzed using high-performance liquid chromatography (HPLC)-diode array detection and HPLC-electrospray ionization tandem mass spectrometry. The potential cytostatic activity of the extract against the human A172 glioblastoma cell line was investigated and the results showed that the extract could decrease cancer cell proliferation and migration. Using cytofluorimetric analyses and caspase-3 assays, the pro-apoptotic action of walnut extract was demonstrated. Furthermore, the evaluation of the antibacterial activity high-lighted the efficacy of the extract in reducing Gram-positive and Gram-negative bacterial growth, most of which were resistant to the antibiotic, ciprofloxacin. Finally, Prediction of Activity Spectra for Substances analysis showed the predicted antitumor and antibacterial activity of HPLC detected compounds. The promising results could provide novel perspective in the field of chemotherapeutic co-adjuvants.

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“…Small amounts of by‐products are able to induce antioxidative responses, for example, by inducing nuclear factor erythroid 2–related factor 2 (Nrf‐2) activity (Tanito & Anderson, 2017). In aged mice, omega fatty acid (eicosapentaenoic acid and docosahexaenoic acid) supplementation has been shown to slow down the degeneration of the retina as well as protecting neural progenitor cells from oxidative stress (Prokopiou et al, 2019). Omega fatty acids belong to the natural antioxidative system of the retina and protect the retina from oxidative stress‐related damages, enhance the activity of other antioxidative mechanisms, for example, glutathione activity and have anti‐inflammatory properties (Lafuente et al, 2021).…”

Section: Review Of the Literaturementioning

confidence: 99%

Regulation of oxidative stress and inflammatory responses in human retinal pigment epithelial cells

Harju

2022

Acta Ophthalmologica

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Age‐related macular degeneration (AMD) is an eye disease, which causes impaired vision that can lead to blindness. The incidence of AMD increases with age. Retinal pigment epithelial (RPE) cells maintain retinal homeostasis and support the functionality of photoreceptors. In the pathogenesis of AMD, the degeneration of the RPE cells precedes photoreceptor cell death. RPE cells are susceptible to oxidative stress, and chronic inflammation involving nucleotide‐binding domain, leucine‐rich repeat and pyrin domain 3 (NLRP3) inflammasome activation and impaired autophagy are challenges faced by aged RPE cells in AMD. There are two types of AMD, dry (85–90%) and wet (10–15%) disease forms. Choroidal neovascularization is typical for wet AMD, and anti‐vascular endothelial growth factor (anti‐VEGF) injections are used to prevent the progression of the disease but there is no curative treatment. There is no cure for the dry disease form, but antioxidants have been proposed as a potential treatment option.Ageing is the most important risk factor of AMD, and tobacco smoke is the most important environmental risk factor that can be controlled. Hydroquinone is a cytotoxic, immunotoxic, carcinogenic and pro‐oxidative component of tobacco smoke. The aim of this PhD thesis was to study hydroquinone‐induced oxidative stress and NLRP3 inflammasome activation in human RPE cells (ARPE‐19 cells). An age‐related eye disease study (AREDS) formulation (incl. omega‐3 fatty acids, vitamin C and E, copper, zinc, lutein and zeaxanthin), which is clinically investigated p.o. dosing combination of dietary supplements for AMD patients, has been evaluated as a possible treatment and restraining option for AMD. Resvega (4.1.1, Table 2) is a similar kind of product to AREDS with added resveratrol, and many of the components incorporated within Resvega can be considered as belonging to the normal antioxidative defence system of the retina. Another aim was to evaluate the effects of Resvega on hydroquinone‐induced oxidative stress or NLRP3 inflammasome activation induced by impaired protein clearance.The results of this study reveal that hydroquinone elevated the activity of NADPH oxidase which subsequently mediated the production of reactive oxygen species (ROS) and predisposed RPE cells to degeneration by reducing levels of vascular endothelial growth factor (VEGF) and pigment epithelium‐derived factor (PEDF). Hydroquinone induced an NLRP3‐independent IL‐18 release and NLRP3 accumulation inside the IL‐1α‐primed cells. Resvega treatment reduced the extent of hydroquinone‐induced ROS production and NLRP3 inflammasome activation evoked by impaired protein clearance. Thus, Resvega alleviated hydroquinone‐ and impaired protein clearance‐induced stress in human RPE cells, but more studies are needed, for example, to reveal the most optimal route of administration for targeting the cells in the retina, since both oxidative stress and NLRP3 inflammasome activation are important contributors to the development of AMD and represent significant treatment targets.

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Omega-3 fatty acids supplementation protects the retina from age-associated degeneration in aged C57BL/6J mice

Cited by 24 publications

References 66 publications

Efficient Enrichment of Retinal DHA with Dietary Lysophosphatidylcholine-DHA: Potential Application for Retinopathies

Efficient Enrichment of Retinal DHA with Dietary Lysophosphatidylcholine-DHA: Potential Application for Retinopathies

The double effect of walnut septum extract (Juglans regia L.) counteracts A172 glioblastoma cell survival and bacterial growth

Regulation of oxidative stress and inflammatory responses in human retinal pigment epithelial cells

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