(Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial Cells
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 aim...
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2024-11-01
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| Series: | Antioxidants |
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| author | Linda M. Bakker Michael E. Boulton Małgorzata B. Różanowska |
| author_facet | Linda M. Bakker Michael E. Boulton Małgorzata B. Różanowska |
| author_sort | Linda M. Bakker |
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| description | 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. |
| format | Article |
| id | doaj-art-b1add18a592346dbbf84b9ec491182b0 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj-art-b1add18a592346dbbf84b9ec491182b02024-11-26T17:47:23ZengMDPI AGAntioxidants2076-39212024-11-011311142810.3390/antiox13111428(Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial CellsLinda M. Bakker0Michael E. Boulton1Małgorzata B. Różanowska2School of Optometry and Vision Sciences, Cardiff University, Cardiff CF24 4HQ, Wales, UKDepartment of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USASchool of Optometry and Vision Sciences, Cardiff University, Cardiff CF24 4HQ, Wales, UKDocosahexaenoate 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.https://www.mdpi.com/2076-3921/13/11/1428docosahexaenoic acidomega-3 fatty acidretinalipid peroxidationretinal pigment epitheliumphotoreceptor outer segments |
| spellingShingle | Linda M. Bakker Michael E. Boulton Małgorzata B. Różanowska (Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial Cells Antioxidants docosahexaenoic acid omega-3 fatty acid retina lipid peroxidation retinal pigment epithelium photoreceptor outer segments |
| title | (Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial Cells |
| title_full | (Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial Cells |
| title_fullStr | (Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial Cells |
| title_full_unstemmed | (Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial Cells |
| title_short | (Photo)toxicity of Partially Oxidized Docosahexaenoate and Its Effect on the Formation of Lipofuscin in Cultured Human Retinal Pigment Epithelial Cells |
| title_sort | photo toxicity of partially oxidized docosahexaenoate and its effect on the formation of lipofuscin in cultured human retinal pigment epithelial cells |
| topic | docosahexaenoic acid omega-3 fatty acid retina lipid peroxidation retinal pigment epithelium photoreceptor outer segments |
| url | https://www.mdpi.com/2076-3921/13/11/1428 |
| work_keys_str_mv | AT lindambakker phototoxicityofpartiallyoxidizeddocosahexaenoateanditseffectontheformationoflipofuscininculturedhumanretinalpigmentepithelialcells AT michaeleboulton phototoxicityofpartiallyoxidizeddocosahexaenoateanditseffectontheformationoflipofuscininculturedhumanretinalpigmentepithelialcells AT małgorzatabrozanowska phototoxicityofpartiallyoxidizeddocosahexaenoateanditseffectontheformationoflipofuscininculturedhumanretinalpigmentepithelialcells |