{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:35:08Z","timestamp":1790627708050,"version":"4.1.0"},"reference-count":40,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"China National Natural Science Foundation","doi-asserted-by":"crossref","award":["81570857"],"award-info":[{"award-number":["81570857"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"China National Natural Science Foundation","doi-asserted-by":"crossref","award":["81271018"],"award-info":[{"award-number":["81271018"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fundamental Research Funds"},{"name":"Medical Science and Technology Program of Zhejiang Province","award":["2016KYA195"],"award-info":[{"award-number":["2016KYA195"]}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology"],"published-print":{"date-parts":[[2016,9]]},"DOI":"10.1016\/j.tox.2016.10.005","type":"journal-article","created":{"date-parts":[[2016,10,17]],"date-time":"2016-10-17T14:16:44Z","timestamp":1476713804000},"page":"41-48","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["All-trans-retinal dimer formation alleviates the cytotoxicity of all-trans-retinal in human retinal pigment epithelial cells"],"prefix":"10.1016","volume":"371","author":[{"given":"Jie","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhui","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingmeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuguo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"11","key":"10.1016\/j.tox.2016.10.005_bib0005","doi-asserted-by":"crossref","first-page":"10422","DOI":"10.1074\/jbc.M312410200","article-title":"Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver","volume":"279","author":"Batten","year":"2004","journal-title":"J. Biol. Chem."},{"issue":"29","key":"10.1016\/j.tox.2016.10.005_bib0010","doi-asserted-by":"crossref","first-page":"24662","DOI":"10.1074\/jbc.M112.354514","article-title":"Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12","volume":"287","author":"Chen","year":"2012","journal-title":"J. Biol. Chem."},{"issue":"7","key":"10.1016\/j.tox.2016.10.005_bib0015","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."},{"issue":"8","key":"10.1016\/j.tox.2016.10.005_bib0020","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1002\/phar.1264","article-title":"Age-related macular degeneration","volume":"33","author":"Cheung","year":"2013","journal-title":"Pharmacotherapy"},{"issue":"9652","key":"10.1016\/j.tox.2016.10.005_bib0025","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1016\/S0140-6736(08)61759-6","article-title":"Age-related macular degeneration","volume":"372","author":"Coleman","year":"2008","journal-title":"Lancet"},{"issue":"4","key":"10.1016\/j.tox.2016.10.005_bib0030","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/S0006-291X(03)01509-2","article-title":"Heme oxygenase-1 expression levels are cell cycle dependent","volume":"308","author":"Colombrita","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"2","key":"10.1016\/j.tox.2016.10.005_bib0035","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1006\/exer.1996.0020","article-title":"ARPE-19, a human retinal pigment epithelial cell line with differentiated properties","volume":"62","author":"Dunn","year":"1996","journal-title":"Exp. Eye Res."},{"issue":"20","key":"10.1016\/j.tox.2016.10.005_bib0040","doi-asserted-by":"crossref","first-page":"7091","DOI":"10.1073\/pnas.0501266102","article-title":"Isolation and characterization of a retinal pigment epithelial cell fluorophore: an all-trans-retinal dimer conjugate","volume":"102","author":"Fishkin","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"13","key":"10.1016\/j.tox.2016.10.005_bib0045","doi-asserted-by":"crossref","first-page":"9478","DOI":"10.1167\/iovs.11-8353","article-title":"Expression and role of VEGF in the adult retinal pigment epithelium","volume":"52","author":"Ford","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"47","key":"10.1016\/j.tox.2016.10.005_bib0050","doi-asserted-by":"crossref","first-page":"45537","DOI":"10.1074\/jbc.M208882200","article-title":"Dual-substrate specificity short chain retinol dehydrogenases from the vertebrate retina","volume":"277","author":"Haeseleer","year":"2002","journal-title":"J. Biol. Chem."},{"issue":"5","key":"10.1016\/j.tox.2016.10.005_bib0055","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s00417-008-0770-2","article-title":"Endoplasmic reticulum stress induced by oxidative stress in retinal pigment epithelial cells","volume":"246","author":"He","year":"2008","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"issue":"15","key":"10.1016\/j.tox.2016.10.005_bib0060","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.1182\/blood-2009-11-256354","article-title":"Overcoming resistance to histone deacetylase inhibitors in human leukemia with the redox modulating compound beta-phenylethyl isothiocyanate","volume":"116","author":"Hu","year":"2010","journal-title":"Blood"},{"issue":"49","key":"10.1016\/j.tox.2016.10.005_bib0065","doi-asserted-by":"crossref","first-page":"19273","DOI":"10.1073\/pnas.0708714104","article-title":"The all-trans-retinal dimer series of lipofuscin pigments in retinal pigment epithelial cells in a recessive Stargardt disease model","volume":"104","author":"Kim","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"21","key":"10.1016\/j.tox.2016.10.005_bib0070","doi-asserted-by":"crossref","first-page":"15326","DOI":"10.1074\/jbc.M112.448712","article-title":"Photoreceptor proteins initiate microglial activation via Toll-like receptor 4 in retinal degeneration mediated by all-trans-retinal","volume":"288","author":"Kohno","year":"2013","journal-title":"J. Biol. Chem."},{"issue":"50","key":"10.1016\/j.tox.2016.10.005_bib0075","doi-asserted-by":"crossref","first-page":"35671","DOI":"10.1074\/jbc.M113.511386","article-title":"Identification of a novel lipofuscin pigment (iisoA2E) in retina and its effects in the retinal pigment epithelial cells","volume":"288","author":"Li","year":"2013","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.tox.2016.10.005_bib0080","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/toxsci\/kfu223","article-title":"Involvement of endoplasmic reticulum stress in all-trans-retinal-induced retinal pigment epithelium degeneration","volume":"143","author":"Li","year":"2015","journal-title":"Toxicol. Sci."},{"issue":"9827","key":"10.1016\/j.tox.2016.10.005_bib0085","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/S0140-6736(12)60282-7","article-title":"Age-related macular degeneration","volume":"379","author":"Lim","year":"2012","journal-title":"Lancet"},{"issue":"38","key":"10.1016\/j.tox.2016.10.005_bib0090","doi-asserted-by":"crossref","first-page":"29354","DOI":"10.1074\/jbc.M910191199","article-title":"The biosynthesis of A2E, a fluorophore of aging retina, involves the formation of the precursor, A2-PE, in the photoreceptor outer segment membrane","volume":"275","author":"Liu","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.tox.2016.10.005_bib0095","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"issue":"39","key":"10.1016\/j.tox.2016.10.005_bib0100","doi-asserted-by":"crossref","first-page":"26684","DOI":"10.1074\/jbc.M804505200","article-title":"Retinopathy in mice induced by disrupted all-trans-retinal clearance","volume":"283","author":"Maeda","year":"2008","journal-title":"J. Biol. Chem."},{"issue":"11","key":"10.1016\/j.tox.2016.10.005_bib0105","doi-asserted-by":"crossref","first-page":"5435","DOI":"10.1167\/iovs.09-3944","article-title":"Limited roles of Rdh8, Rdh12, and Abca4 in all-trans-retinal clearance in mouse retina","volume":"50","author":"Maeda","year":"2009","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"22","key":"10.1016\/j.tox.2016.10.005_bib0110","doi-asserted-by":"crossref","first-page":"15173","DOI":"10.1074\/jbc.M900322200","article-title":"Involvement of all-trans-retinal in acute light-induced retinopathy of mice","volume":"284","author":"Maeda","year":"2009","journal-title":"J. Biol. Chem."},{"issue":"10","key":"10.1016\/j.tox.2016.10.005_bib0115","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":"Invest. Ophthalmol. Vis. Sci."},{"issue":"6","key":"10.1016\/j.tox.2016.10.005_bib0120","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."},{"issue":"6","key":"10.1016\/j.tox.2016.10.005_bib0125","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1111\/j.1751-1097.2012.01129.x","article-title":"All-trans retinal mediates light-induced oxidation in single living rod photoreceptors","volume":"88","author":"Masutomi","year":"2012","journal-title":"Photochem. Photobiol."},{"issue":"35","key":"10.1016\/j.tox.2016.10.005_bib0130","doi-asserted-by":"crossref","first-page":"12413","DOI":"10.1073\/pnas.0503460102","article-title":"RPE65 is the isomerohydrolase in the retinoid visual cycle","volume":"102","author":"Moiseyev","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"7","key":"10.1016\/j.tox.2016.10.005_bib0135","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.bbalip.2009.02.004","article-title":"The role of the photoreceptor ABC transporter ABCA4 in lipid transport and Stargardt macular degeneration","volume":"1791","author":"Molday","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"issue":"7","key":"10.1016\/j.tox.2016.10.005_bib0140","doi-asserted-by":"crossref","first-page":"4536","DOI":"10.1074\/jbc.M207293200","article-title":"Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26S proteasome","volume":"278","author":"Nguyen","year":"2003","journal-title":"J. Biol. Chem."},{"issue":"25","key":"10.1016\/j.tox.2016.10.005_bib0145","doi-asserted-by":"crossref","first-page":"14609","DOI":"10.1073\/pnas.95.25.14609","article-title":"Isolation and one-step preparation of A2E and iso-A2E, fluorophores from human retinal pigment epithelium","volume":"95","author":"Parish","year":"1998","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"6","key":"10.1016\/j.tox.2016.10.005_bib0150","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.exer.2010.08.013","article-title":"Retinol dehydrogenases (RDHs) in the visual cycle","volume":"91","author":"Parker","year":"2010","journal-title":"Exp. Eye Res."},{"issue":"7","key":"10.1016\/j.tox.2016.10.005_bib0155","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1021\/cr960141c","article-title":"The biochemistry of the visual cycle","volume":"101","author":"Rando","year":"2001","journal-title":"Chem. Rev."},{"key":"10.1016\/j.tox.2016.10.005_bib0160","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1146\/annurev-nutr-071811-150748","article-title":"Vitamin A metabolism in rod and cone visual cycles","volume":"32","author":"Saari","year":"2012","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.tox.2016.10.005_bib0165","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."},{"issue":"17","key":"10.1016\/j.tox.2016.10.005_bib0170","doi-asserted-by":"crossref","first-page":"15543","DOI":"10.1074\/jbc.M111.228551","article-title":"Toll-like receptor 3 is required for development of retinopathy caused by impaired all-trans-retinal clearance in mice","volume":"286","author":"Shiose","year":"2011","journal-title":"J. Biol. Chem."},{"issue":"4","key":"10.1016\/j.tox.2016.10.005_bib0175","first-page":"1222","article-title":"Involvement of oxidative mechanisms in blue-light-induced damage to A2E-laden RPE","volume":"43","author":"Sparrow","year":"2002","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.tox.2016.10.005_bib0180","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/978-0-387-74904-4_46","article-title":"A2E, a pigment of RPE lipofuscin, is generated from the precursor, A2PE, by a lysosomal enzyme activity","volume":"613","author":"Sparrow","year":"2008","journal-title":"Recent Adv. Retin. Degeneration"},{"issue":"2","key":"10.1016\/j.tox.2016.10.005_bib0185","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1194\/jlr.R000687","article-title":"Phospholipid meets all-trans-retinal: the making of RPE bisretinoids","volume":"51","author":"Sparrow","year":"2010","journal-title":"J. Lipid Res."},{"issue":"2","key":"10.1016\/j.tox.2016.10.005_bib0190","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.preteyeres.2011.12.001","article-title":"The bisretinoids of retinal pigment epithelium","volume":"31","author":"Sparrow","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"issue":"16","key":"10.1016\/j.tox.2016.10.005_bib0195","doi-asserted-by":"crossref","first-page":"7275","DOI":"10.1073\/pnas.0913112107","article-title":"Structural characterization of bisretinoid A2E photocleavage products and implications for age-related macular degeneration","volume":"107","author":"Wu","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"1\u20133","key":"10.1016\/j.tox.2016.10.005_bib0200","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ejphar.2012.01.006","article-title":"Asiatic acid protects primary neurons against C2-ceramide-induced apoptosis","volume":"679","author":"Zhang","year":"2012","journal-title":"Eur. J. Pharmacol."}],"container-title":["Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X16302402?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X16302402?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T23:33:02Z","timestamp":1759534382000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0300483X16302402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9]]},"references-count":40,"alternative-id":["S0300483X16302402"],"URL":"https:\/\/doi.org\/10.1016\/j.tox.2016.10.005","relation":{},"ISSN":["0300-483X"],"issn-type":[{"value":"0300-483X","type":"print"}],"subject":[],"published":{"date-parts":[[2016,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"All-trans-retinal dimer formation alleviates the cytotoxicity of all-trans-retinal in human retinal pigment epithelial cells","name":"articletitle","label":"Article Title"},{"value":"Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tox.2016.10.005","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Elsevier Ireland Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}