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(Photo)toxicity of partially oxidized docosahexaenoate and its effect on the formation of lipofuscin in cultured human retinal pigment epithelial cells

Bakker, Linda M., Boulton, Michael E. and Różanowska, Małgorzata B. ORCID: https://orcid.org/0000-0003-2913-8954 2024. (Photo)toxicity of partially oxidized docosahexaenoate and its effect on the formation of lipofuscin in cultured human retinal pigment epithelial cells. Antioxidants 13 (11) , 1428. 10.3390/antiox13111428

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Abstract

Docosahexaenoate is a cytoprotective ω-3 polyunsaturated lipid that is abundant in the retina and is essential for its function. Due to its six unsaturated double bonds, docosahexaenoate is highly susceptible to oxidation and the formation of products with photosensitizing properties. This study aimed to test on cultured human retinal pigment epithelial cells ARPE-19 the (photo)cytotoxic potential of partly oxidized docosahexaenoate and its effect on the formation of lipofuscin from phagocytosed photoreceptor outer segments (POSs). The results demonstrate that the cytoprotective effects of docosahexaenoate do not counteract the deleterious effects of its oxidation products, leading to the concentration-dependent loss of cell metabolic activity, which is exacerbated by concomitant exposure to visible light. Partly oxidized docosahexaenoate does not cause permeability of the cell plasma membrane but does cause apoptosis. While vitamin E can provide partial protection from the (photo)toxicity of partly oxidized docosahexaenoate, zeaxanthin undergoes rapid photodegradation and can exacerbate the (photo)toxicity. Feeding cells with POSs enriched in partly oxidized docosahexaenoate results in a greater accumulation of intracellular fluorescent lipofuscin than in cells fed POSs without the addition. In conclusion, partly oxidized docosahexaenoate increases the accumulation of lipofuscin-like intracellular deposits, is cytotoxic, and its toxicity increases during exposure to light. These effects may contribute to the increased progression of geographic atrophy observed after long-term supplementation with docosahexaenoate in age-related macular degeneration patients.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Optometry and Vision Sciences
Additional Information: License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Start Date: 2024-11-20
Publisher: MDPI
ISSN: 2076-3921
Date of First Compliant Deposit: 3 December 2024
Date of Acceptance: 19 November 2024
Last Modified: 03 Dec 2024 17:30
URI: https://orca.cardiff.ac.uk/id/eprint/174471

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