{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T13:58:36Z","timestamp":1773064716388,"version":"3.50.1"},"reference-count":105,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education\/State Committee for Scientific Research, Poland","award":["PB 6PO4A 06217"],"award-info":[{"award-number":["PB 6PO4A 06217"]}]},{"name":"Ministry of Science and Higher Education\/State Committee for Scientific Research, Poland","award":["3P04A 044 23"],"award-info":[{"award-number":["3P04A 044 23"]}]},{"name":"Wellcome Trust","award":["PB 6PO4A 06217"],"award-info":[{"award-number":["PB 6PO4A 06217"]}]},{"name":"Wellcome Trust","award":["3P04A 044 23"],"award-info":[{"award-number":["3P04A 044 23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Vitamins C and E and zeaxanthin are components of a supplement tested in a large clinical trial\u2014Age-Related Eye Disease Study 2 (AREDS2)\u2014and 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 \u03b1-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 \u00b5M zeaxanthin and 80 \u00b5M \u03b1-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 \u03b1-tocopherol partly ameliorated the cytotoxic effects. Altogether, our results suggest that the optimal combination includes upper levels of zeaxanthin and \u03b1-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.<\/jats:p>","DOI":"10.3390\/antiox11061132","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T10:49:14Z","timestamp":1654771754000},"page":"1132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["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?"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2913-8954","authenticated-orcid":false,"given":"Ma\u0142gorzata B.","family":"R\u00f3\u017canowska","sequence":"first","affiliation":[{"name":"School of Optometry and Vision Sciences, Cardiff University, Cardiff CF24 4HQ, Wales, UK"},{"name":"Cardiff Institute for Tissue Engineering and Repair (CITER), Cardiff University, Cardiff CF24 4HQ, Wales, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Czuba-Pe\u0142ech","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6362-1758","authenticated-orcid":false,"given":"Bartosz","family":"R\u00f3\u017canowski","sequence":"additional","affiliation":[{"name":"Institute of Biology, Pedagogical University, 30-084 Krak\u00f3w, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1562\/2004-11-13-IR-371","article-title":"Light-induced damage to the retina: Role of rhodopsin chromophore revisited","volume":"81","author":"Rozanowska","year":"2005","journal-title":"Photochem. Photobiol."},{"key":"ref_2","unstructured":"Tombran-Tink, J., and Barnstable, C.J. (2008). Visual transduction and age-related changes in lipofuscin. Ophthalmology Research: The Visual Transduction Cascade, The Humana Press Inc."},{"key":"ref_3","unstructured":"Smith, K.C. (2009). Photobiology of the retina: Light damage to the retina. Photobiological Sciences, American Society for Photobiology. Available online: http:\/\/www.photobiology.info."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1111\/j.1751-1097.2012.01143.x","article-title":"Retinal photodamage mediated by all-trans-retinal","volume":"88","author":"Maeda","year":"2012","journal-title":"Photochem. Photobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1021\/cr400107q","article-title":"Chemistry of the retinoid (visual) cycle","volume":"114","author":"Kiser","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nchembio.759","article-title":"Primary amines protect against retinal degeneration in mouse models of retinopathies","volume":"8","author":"Maeda","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5059","DOI":"10.1074\/jbc.M111.315432","article-title":"Mechanism of all-trans-retinal toxicity with implications for Stargardt disease and age-related macular degeneration","volume":"287","author":"Chen","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev-vision-111815-114407","article-title":"Retinoids and Retinal Diseases","volume":"2","author":"Kiser","year":"2016","journal-title":"Annu. Rev. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10207","DOI":"10.1038\/s41598-018-28254-8","article-title":"Blue light excited retinal intercepts cellular signaling","volume":"8","author":"Ratnayake","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"109547","DOI":"10.1016\/j.cellsig.2020.109547","article-title":"Blue light-triggered photochemistry and cytotoxicity of retinal","volume":"69","author":"Ratnayake","year":"2020","journal-title":"Cell Signal"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/S0891-5849(97)00395-X","article-title":"Blue light-induced singlet oxygen generation by retinal lipofuscin in non-polar media","volume":"24","author":"Rozanowska","year":"1998","journal-title":"Free Radic. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1111\/j.1751-1097.1996.tb05673.x","article-title":"The photochemistry of the retinoids as studied by steady-state and pulsed methods","volume":"63","author":"Dillon","year":"1996","journal-title":"PhotoChem. PhotoBiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e163","DOI":"10.1016\/j.ddmod.2014.01.001","article-title":"Retinal degeneration in animal models with a defective visual cycle","volume":"10","author":"Maeda","year":"2013","journal-title":"Drug Discov. Today Dis. Models"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Sahu, B., and Maeda, A. (2016). Retinol Dehydrogenases Regulate Vitamin A Metabolism for Visual Function. Nutrients, 8.","DOI":"10.3390\/nu8110746"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Molday, R.S., Garces, F.A., Scortecci, J.F., and Molday, L.L. (Prog. Retin. Eye Res., 2021). Structure and function of ABCA4 and its role in the visual cycle and Stargardt macular degeneration, Prog. Retin. Eye Res., in press.","DOI":"10.1016\/j.preteyeres.2021.101036"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1021\/acs.bioconjchem.1c00043","article-title":"Peptide Derivatives of Retinylamine Prevent Retinal Degeneration with Minimal Side Effects on Vision in Mice","volume":"32","author":"Yu","year":"2021","journal-title":"Bioconjug Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.biomaterials.2014.12.019","article-title":"Prolonged prevention of retinal degeneration with retinylamine loaded nanoparticles","volume":"44","author":"Puntel","year":"2015","journal-title":"Biomaterials"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.1021\/bm501352s","article-title":"Multifunctional PEG retinylamine conjugate provides prolonged protection against retinal degeneration in mice","volume":"15","author":"Yu","year":"2014","journal-title":"Biomacromolecules"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.exer.2014.04.003","article-title":"All-trans-retinal induces Bax activation via DNA damage to mediate retinal cell apoptosis","volume":"123","author":"Sawada","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"E1428","DOI":"10.1073\/pnas.1317986111","article-title":"Two-photon microscopy reveals early rod photoreceptor cell damage in light-exposed mutant mice","volume":"111","author":"Maeda","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1001\/archopht.121.8.1099","article-title":"Maculas affected by age-related macular degeneration contain increased chelatable iron in the retinal pigment epithelium and Bruch\u2019s membrane","volume":"121","author":"Hahn","year":"2003","journal-title":"Arch. OphthalMol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1074\/mcp.M700525-MCP200","article-title":"Retinal pigment epithelium lipofuscin proteomics","volume":"7","author":"Ng","year":"2008","journal-title":"Mol. Cell Proteom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/978-1-4419-1399-9_47","article-title":"Proteomic and genomic biomarkers for age-related macular degeneration","volume":"664","author":"Gu","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.exer.2015.05.019","article-title":"Iron accumulation in Bruch\u2019s membrane and melanosomes of donor eyes with age-related macular degeneration","volume":"137","author":"Biesemeier","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Toma, C., De Cilla, S., Palumbo, A., Garhwal, D.P., and Grossini, E. (2021). Oxidative and Nitrosative Stress in Age-Related Macular Degeneration: A Review of Their Role in Different Stages of Disease. Antioxidants, 10.","DOI":"10.3390\/antiox10050653"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ruan, Y., Jiang, S., and Gericke, A. (2021). Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031296"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Romero-Vazquez, S., Llorens, V., Soler-Boronat, A., Figueras-Roca, M., Adan, A., and Molins, B. (2021). Interlink between Inflammation and Oxidative Stress in Age-Related Macular Degeneration: Role of Complement Factor H. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070763"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108513","DOI":"10.1016\/j.neuropharm.2021.108513","article-title":"New insights into oxidative stress and immune mechanisms involved in age-related macular degeneration tackled by novel therapies","volume":"188","author":"Potilinski","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41572-021-00265-2","article-title":"Age-related macular degeneration","volume":"7","author":"Fleckenstein","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Jadeja, R.N., and Martin, P.M. (2021). Oxidative Stress and Inflammation in Retinal Degeneration. Antioxidants, 10.","DOI":"10.3390\/antiox10050790"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/0042-6989(85)90123-3","article-title":"Preliminary identification of the human macular pigment","volume":"25","author":"Bone","year":"1985","journal-title":"Vision Res."},{"key":"ref_32","unstructured":"Landrum, J. (2010). The functional role of xanthophylls in the primate retina. Carotenoids Physical, Chemichal, and Biological Functions and Properties, CRC Press."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1093\/advances\/nmy025","article-title":"Intrinsic and extrinsic factors impacting absorption, metabolism, and health effects of dietary carotenoids","volume":"9","author":"Moran","year":"2018","journal-title":"Adv. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Widomska, J., SanGiovanni, J.P., and Subczynski, W.K. (2020). Why is zeaxanthin the most concentrated xanthophyll in the central fovea?. Nutrients, 12.","DOI":"10.3390\/nu12051333"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"158617","DOI":"10.1016\/j.bbalip.2020.158617","article-title":"The macular carotenoids: A biochemical overview","volume":"1865","author":"Arunkumar","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e2200068119","DOI":"10.1073\/pnas.2200068119","article-title":"Aster proteins mediate carotenoid transport in mammalian cells","volume":"119","author":"Bandara","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100864","DOI":"10.1016\/j.preteyeres.2020.100864","article-title":"Molecular components affecting ocular carotenoid and retinoid homeostasis","volume":"80","author":"Moon","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1076\/ceyr.19.6.491.5276","article-title":"Lutein and zeaxanthin are associated with photoreceptors in the human retina","volume":"19","author":"Sommerburg","year":"1999","journal-title":"Curr. Eye Res."},{"key":"ref_39","first-page":"1200","article-title":"Lutein and zeaxanthin concentrations in rod outer segment membranes from perifoveal and peripheral human retina","volume":"41","author":"Rapp","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/joa.12641","article-title":"Determination of retinal surface area","volume":"231","author":"Nagra","year":"2017","journal-title":"J. Anat."},{"key":"ref_41","unstructured":"Rodieck, R.W. (1998). The First Steps in Seeing; Sinauer Associates, Oxford University Press."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Black, H.S., Boehm, F., Edge, R., and Truscott, T.G. (2020). The Benefits and Risks of Certain Dietary Carotenoids that Exhibit both Anti- and Pro-Oxidative Mechanisms\u2014A Comprehensive Review. Antioxidants, 9.","DOI":"10.3390\/antiox9030264"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Edge, R., and Truscott, T.G. (2018). Singlet oxygen and free radical reactions of retinoids and carotenoids-A review. Antioxidants, 7.","DOI":"10.3390\/antiox7010005"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rozanowska, M.B., Czuba-Pelech, B., Landrum, J.T., and Rozanowski, B. (2021). Comparison of Antioxidant Properties of Dehydrolutein with Lutein and Zeaxanthin, and their Effects on Cultured Retinal Pigment Epithelial Cells. Antioxidants, 10.","DOI":"10.20944\/preprints202104.0066.v1"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbabio.2005.05.008","article-title":"Cyclic endoperoxides of beta-carotene, potential pro-oxidants, as products of chemical quenching of singlet oxygen","volume":"1709","author":"Fiedor","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_46","unstructured":"Landrum, J.T. (2010). Uptake and photoprotection in cultured RPE cells. Carotenoids: Physical, Chemical, and Biological Functions and Properties, CRC Press."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3390\/nu6020466","article-title":"Potential role of carotenoids as antioxidants in human health and disease","volume":"6","author":"Fiedor","year":"2014","journal-title":"Nutrients"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0003-9861(90)90556-E","article-title":"Physical and chemical scavenging of singlet molecular oxygen by tocopherols","volume":"277","author":"Kaiser","year":"1990","journal-title":"Arch. BioChem. Biophys."},{"key":"ref_49","unstructured":"Halliwell, B., and Gutteridge, J.M.C. (2007). Free Radicals in Biology and Medicine, Oxford University Press. [4th ed.]."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Rozanowska, M., Edge, R., Land, E.J., Navaratnam, S., Sarna, T., and Truscott, T.G. (2019). Scavenging of Retinoid Cation Radicals by Urate, Trolox, and alpha-, beta-, gamma-, and delta-Tocopherols. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112799"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.freeradbiomed.2014.03.035","article-title":"Natural forms of vitamin E: Metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy","volume":"72","author":"Jiang","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/00006982-198200000-00012","article-title":"The roles of vitamin E and unsaturated fatty acids in the visual process","volume":"2","author":"Robison","year":"1982","journal-title":"Retina"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"693","DOI":"10.3109\/02713689508998497","article-title":"Vitamin E in macular and peripheral tissues of the human eye","volume":"14","author":"Friedrichson","year":"1995","journal-title":"Curr. Eye Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.3109\/02713688709034876","article-title":"Vitamin E in human neural retina and retinal pigment epithelium: Effect of age","volume":"6","author":"Organisciak","year":"1987","journal-title":"Curr. Eye Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Jungert, A., and Neuhauser-Berthold, M. (2020). Interrelation between Plasma Concentrations of Vitamins C and E along the Trajectory of Ageing in Consideration of Lifestyle and Body Composition: A Longitudinal Study over Two Decades. Nutrients, 12.","DOI":"10.3390\/nu12102944"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Stuetz, W., Weber, D., Dolle, M.E.T., Jansen, E., Grubeck-Loebenstein, B., Fiegl, S., Toussaint, O., Bernhardt, J., Gonos, E.S., and Franceschi, C. (2016). Plasma Carotenoids, Tocopherols, and Retinol in the Age-Stratified (35\u201374 Years) General Population: A Cross-Sectional Study in Six European Countries. Nutrients, 8.","DOI":"10.3390\/nu8100614"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lykkesfeldt, J., and Tveden-Nyborg, P. (2019). The Pharmacokinetics of Vitamin C. Nutrients, 11.","DOI":"10.3390\/nu11102412"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1167\/iovs.16-19162","article-title":"Expression Profiling of Ascorbic Acid-Related Transporters in Human and Mouse Eyes","volume":"57","author":"Ma","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3945\/an.110.000109","article-title":"Vitamin C: A concentration-function approach yields pharmacology and therapeutic discoveries","volume":"2","author":"Levine","year":"2011","journal-title":"Adv. Nutr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/S0306-4522(97)00347-3","article-title":"Differential compartmentalization of brain ascorbate and glutathione between neurons and glia","volume":"82","author":"Rice","year":"1998","journal-title":"Neuroscience"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7454","DOI":"10.1021\/jp990838c","article-title":"Quenching of singlet oxygen by Trolox C, ascorbate, and amino acids: Effects of pH and temperature","volume":"103","author":"Bisby","year":"1999","journal-title":"J. Phys. Chem. A"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3109\/02713689509033513","article-title":"Endogenous ascorbate regenerates vitamin E in the retina directly and in combination with exogenous dihydrolipoic acid","volume":"14","author":"Stoyanovsky","year":"1995","journal-title":"Curr. Eye Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/j.freeradbiomed.2003.07.005","article-title":"Cooperation of antioxidants in protection against photosensitized oxidation","volume":"35","author":"Wrona","year":"2003","journal-title":"Free Radic. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/j.freeradbiomed.2004.02.005","article-title":"Zeaxanthin in combination with ascorbic acid or alpha-tocopherol protects ARPE-19 cells against photosensitized peroxidation of lipids","volume":"36","author":"Wrona","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1111\/j.1751-1097.2012.01228.x","article-title":"Concentration dependence of vitamin C in combinations with vitamin E and zeaxanthin on light-induced toxicity to retinal pigment epithelial cells","volume":"88","author":"Rozanowska","year":"2012","journal-title":"Photochem. Photobiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1016\/j.ophtha.2012.05.027","article-title":"The Age-Related Eye Disease Study 2 (AREDS2): Study design and baseline characteristics (AREDS2 report number 1)","volume":"119","author":"Group","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Age-Related Eye Disease Study 2 Research Group (2013). Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: The Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA, 309, 2005\u20132015.","DOI":"10.1001\/jama.2013.4997"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Age-Related Eye Disease Study 2 Research Group, Chew, E.Y., Clemons, T.E., Sangiovanni, J.P., Danis, R.P., Ferris, F.L., Elman, M.J., Antoszyk, A.N., Ruby, A.J., and Orth, D. (2014). Secondary analyses of the effects of lutein\/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmol., 132, 142\u2013149.","DOI":"10.1001\/jamaophthalmol.2013.7376"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1167\/iovs.06-0558","article-title":"HPLC measurement of ocular carotenoid levels in human donor eyes in the lutein supplementation era","volume":"48","author":"Bhosale","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1167\/iovs.13-13216","article-title":"Genetic evidence for role of carotenoids in age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS)","volume":"55","author":"Meyers","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.cell.2018.08.033","article-title":"Aster Proteins Facilitate Nonvesicular Plasma Membrane to ER Cholesterol Transport in Mammalian Cells","volume":"175","author":"Sandhu","year":"2018","journal-title":"Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"9961","DOI":"10.2147\/IJN.S276355","article-title":"Pharmacology and Pharmacokinetics of Vitamin E: Nanoformulations to Enhance Bioavailability","volume":"15","author":"Ng","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1093\/ajcn\/nqz172","article-title":"Vitamin E absorption and kinetics in healthy women, as modulated by food and by fat, studied using 2 deuterium-labeled alpha-tocopherols in a 3-phase crossover design","volume":"110","author":"Traber","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1111\/j.1751-1097.2012.01161.x","article-title":"Cytotoxicity of all-trans-retinal increases upon photodegradation","volume":"88","author":"Rozanowska","year":"2012","journal-title":"Photochem. Photobiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/j.freeradbiomed.2005.07.018","article-title":"Pulse radiolysis study of the interaction of retinoids with peroxyl radicals","volume":"39","author":"Rozanowska","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1001\/archophthalmol.2008.621","article-title":"The gel state of the vitreous and ascorbate-dependent oxygen consumption: Relationship to the etiology of nuclear cataracts","volume":"127","author":"Shui","year":"2009","journal-title":"Arch. OphthalMol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1111\/j.1751-1097.2007.00291.x","article-title":"The pro-oxidant effects of interactions of ascorbate with photoexcited melanin fade away with aging of the retina","volume":"84","author":"Rozanowski","year":"2008","journal-title":"Photochem. Photobiol."},{"key":"ref_78","first-page":"2088","article-title":"Photoreactivity of aged human RPE melanosomes: A comparison with lipofuscin","volume":"43","author":"Rozanowska","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1111\/j.1751-1097.1997.tb08593.x","article-title":"The role of retinal pigment epithelium melanin in photoinduced oxidation of ascorbate","volume":"65","author":"Rozanowska","year":"1997","journal-title":"PhotoChem. PhotoBiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.1167\/iovs.09-3581","article-title":"Evaluation of potential therapies for a mouse model of human age-related macular degeneration caused by delayed all-trans-retinal clearance","volume":"50","author":"Maeda","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3109\/02713689209001774","article-title":"The effects of L-and D-ascorbic acid administration on retinal tissue levels and light damage in rats","volume":"11","author":"Organisciak","year":"1992","journal-title":"Curr. Eye Res."},{"key":"ref_82","first-page":"2814","article-title":"Ascorbate treatment prevents accumulation of phagosomes in RPE in light damage","volume":"33","author":"Blanks","year":"1992","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_83","first-page":"1195","article-title":"The protective effect of ascorbic acid in retinal light damage of rats exposed to intermittent light","volume":"31","author":"Organisciak","year":"1990","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_84","first-page":"455","article-title":"Aspects of the ascorbate protective mechanism in retinal light damage of rats with normal and reduced ROS docosahexaenoic acid","volume":"247","author":"Organisciak","year":"1987","journal-title":"Prog. Clin. Biol. Res."},{"key":"ref_85","first-page":"469","article-title":"Ascorbate and dietary protective mechanisms in retinal light damage of rats: Electrophysiological, histological and DNA measurements","volume":"247","author":"Noell","year":"1987","journal-title":"Prog. Clin. Biol. Res."},{"key":"ref_86","first-page":"1580","article-title":"The protective effect of ascorbate in retinal light damage of rats","volume":"26","author":"Organisciak","year":"1985","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_87","first-page":"1589","article-title":"Amelioration of photic injury in rat retina by ascorbic acid: A histopathologic study","volume":"26","author":"Li","year":"1985","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"257","DOI":"10.3109\/02713688408997208","article-title":"Ascorbate and glutathione levels in the developing normal and dystrophic rat retina: Effect of intense light exposure","volume":"3","author":"Organisciak","year":"1984","journal-title":"Curr. Eye Res."},{"key":"ref_89","first-page":"862","article-title":"Reduced and oxidized ascorbates in guinea pig retina under normal and light-exposed conditions","volume":"24","author":"Woodford","year":"1983","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1080\/10715762.2017.1380307","article-title":"Lipofuscin-mediated photic stress inhibits phagocytic activity of ARPE-19 cells; effect of donors\u2019 age and antioxidants","volume":"51","author":"Olchawa","year":"2017","journal-title":"Free Radic. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1111\/pcmr.12914","article-title":"The effect of aging and antioxidants on photoreactivity and phototoxicity of human melanosomes: An in vitro study","volume":"34","author":"Olchawa","year":"2020","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Olchawa, M.M., Szewczyk, G.M., Zadlo, A.C., Sarna, M.W., Wnuk, D., and Sarna, T.J. (2020). The Effect of Antioxidants on Photoreactivity and Phototoxic Potential of RPE Melanolipofuscin Granules from Human Donors of Different Age. Antioxidants, 9.","DOI":"10.3390\/antiox9111044"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1011-1344(01)00111-7","article-title":"Characterisation of carotenoid radical cations in liposomal environments: Interaction with vitamin C","volume":"60","author":"Burke","year":"2001","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1136\/bjo.63.3.181","article-title":"Convolution in human rods: An ageing process","volume":"63","author":"Marshall","year":"1979","journal-title":"Br. J. OphthalMol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Rychlicka, M., Niezgoda, N., and Gliszczynska, A. (2018). Lipase-Catalyzed Acidolysis of Egg-Yolk Phosphatidylcholine with Citronellic Acid. New Insight into Synthesis of Isoprenoid-Phospholipids. Molecules, 23.","DOI":"10.3390\/molecules23020314"},{"key":"ref_96","first-page":"1433","article-title":"Lipids in human lipofuscin-enriched subcellular fractions of two age populations","volume":"31","author":"Bazan","year":"1990","journal-title":"Comp. Rod Outer Segm. Neural Retina. Investig. Ophthalmol. Vis. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0014-4835(89)80080-6","article-title":"Glutathione-dependent enzymes in intact rod outer segments","volume":"48","author":"Naash","year":"1989","journal-title":"Exp. Eye Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1167\/iovs.02-0191","article-title":"Glutathione peroxidase induced in rat retinas to counteract photic injury","volume":"44","author":"Ohira","year":"2003","journal-title":"Investig. OphthalMol. Vis. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2613","DOI":"10.1167\/iovs.05-0962","article-title":"Retinal light damage: Structural and functional effects of the antioxidant glutathione peroxidase-1","volume":"47","author":"Gosbell","year":"2006","journal-title":"Investig. Ophthalmol. Vis Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5168","DOI":"10.1167\/iovs.07-0037","article-title":"Lutein and zeaxanthin protect photoreceptors from apoptosis induced by oxidative stress: Relation with docosahexaenoic acid","volume":"48","author":"Chucair","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"112425","DOI":"10.1016\/j.jphotobiol.2022.112425","article-title":"Deuterated polyunsaturated fatty acids inhibit photoirradiation-induced lipid peroxidation in lipid bilayers","volume":"229","author":"Firsov","year":"2022","journal-title":"J. PhotoChem. PhotoBiol. B"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.exer.2007.09.010","article-title":"Carotenoid derived aldehydes-induced oxidative stress causes apoptotic cell death in human retinal pigment epithelial cells","volume":"86","author":"Kalariya","year":"2008","journal-title":"Exp. Eye Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1021\/ja410569g","article-title":"Unusual kinetic isotope effects of deuterium reinforced polyunsaturated fatty acids in tocopherol-mediated free radical chain oxidations","volume":"136","author":"Lamberson","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/S0014-5793(01)02601-1","article-title":"One-electron reduction potentials of dietary carotenoid radical cations in aqueous micellar environments","volume":"500","author":"Burke","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1002\/jms.868","article-title":"Electrospray tandem mass spectrometric analysis of zeaxanthin and its oxidation products","volume":"40","author":"Prasain","year":"2005","journal-title":"J. Mass Spectrom."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/6\/1132\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:27:09Z","timestamp":1760138829000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/6\/1132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,9]]},"references-count":105,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["antiox11061132"],"URL":"https:\/\/doi.org\/10.3390\/antiox11061132","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,9]]}}}