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?

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:	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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