Rozanowska, Malgorzata B.  ORCID: https://orcid.org/0000-0003-2913-8954, Czuba-Pelech, Barbara and Rózanowski, Bartosz
2022.
Is there an optimal combination of AREDS2 antioxidants zeaxanthin, vitamin E and vitamin C on light-induced toxicity of Vitamin A aldehyde to the retina?
Antioxidants
11
(6)
, 1132.
10.3390/antiox11061132
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Abstract
Vitamins C and E and zeaxanthin are components of a supplement tested in a large clinical trial—Age-Related Eye Disease Study 2 (AREDS2)—and it has been demonstrated that they can inhibit the progression of age-related macular degeneration. The aim of this study was to determine the optimal combinations of these antioxidants to prevent the phototoxicity mediated by vitamin A aldehyde (ATR), which can accumulate in photoreceptor outer segments (POS) upon exposure to light. We used cultured retinal pigment epithelial cells ARPE-19 and liposomes containing unsaturated lipids and ATR as a model of POS. Cells and/or liposomes were enriched with lipophilic antioxidants, whereas ascorbate was added just before the exposure to light. Supplementing the cells and/or liposomes with single lipophilic antioxidants had only a minor effect on phototoxicity, but the protection substantially increased in the presence of both ways of supplementation. Combinations of zeaxanthin with α-tocopherol in liposomes and cells provided substantial protection, enhancing cell viability from ~26% in the absence of antioxidants to ~63% in the presence of 4 µM zeaxanthin and 80 µM α-tocopherol, and this protective effect was further increased to ~69% in the presence of 0.5 mM ascorbate. The protective effect of ascorbate disappeared at a concentration of 1 mM, whereas 2 mM of ascorbate exacerbated the phototoxicity. Zeaxanthin or α-tocopherol partly ameliorated the cytotoxic effects. Altogether, our results suggest that the optimal combination includes upper levels of zeaxanthin and α-tocopherol achievable by diet and/or supplementations, whereas ascorbate needs to be at a four-fold smaller concentration than that in the vitreous. The physiological relevance of the results is discussed.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Optometry and Vision Sciences |
| Additional Information: | This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Publisher: | MDPI |
| ISSN: | 2076-3921 |
| Funders: | Wellcome Trust, Ministry of Science and Higher Education/State Committee for Scientific Research Poland |
| Date of First Compliant Deposit: | 12 June 2022 |
| Date of Acceptance: | 6 June 2022 |
| Last Modified: | 04 Sep 2023 19:03 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/150436 |
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