{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:54:44Z","timestamp":1787064884375,"version":"build-2736575974"},"reference-count":79,"publisher":"Elsevier BV","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,7,25]],"date-time":"2020-07-25T00:00:00Z","timestamp":1595635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003802","name":"University Research Committee, University of Hong Kong","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003802","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2020,12]]},"DOI":"10.1016\/j.ymthe.2020.07.024","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T22:36:24Z","timestamp":1595630184000},"page":"2642-2661","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":41,"title":["PSCs Reveal PUFA-Provoked Mitochondrial Stress as a Central Node Potentiating RPE Degeneration in Bietti\u2019s Crystalline Dystrophy"],"prefix":"10.1016","volume":"28","author":[{"given":"Zhao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peikai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengqin","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Fat","family":"Tse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8189-7160","authenticated-orcid":false,"given":"Qizhou","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2020.07.024_bib1","first-page":"737","article-title":"Uber familiares Vorkommen von \u201cRetinitis punctata albescens\u201d (verbunden mit \u201cDystrophia marginalis cristalinea corneae\u201d). Glitzen des Glaskorpers und anderen degenerativen Augenveranderungen","volume":"99","author":"Bietti","year":"1937","journal-title":"Lin. Mbl. Augenh."},{"key":"10.1016\/j.ymthe.2020.07.024_bib2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3109\/13816818309007148","article-title":"Ophthalmic genetics in China","volume":"2","author":"Hu","year":"1983","journal-title":"Ophthalmic Paediatr. Genet."},{"key":"10.1016\/j.ymthe.2020.07.024_bib3","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1001\/archopht.1989.01070010219026","article-title":"Bietti\u2019s crystalline dystrophy. A clinicopathologic correlative study","volume":"107","author":"Wilson","year":"1989","journal-title":"Arch. Ophthalmol."},{"key":"10.1016\/j.ymthe.2020.07.024_bib4","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.ophtha.2013.11.042","article-title":"Detailed phenotypic and genotypic characterization of Bietti crystalline dystrophy","volume":"121","author":"Halford","year":"2014","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ymthe.2020.07.024_bib5","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1136\/bjo.2010.199356","article-title":"Outer retinal circular structures in patients with Bietti crystalline retinopathy","volume":"96","author":"Kojima","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"10.1016\/j.ymthe.2020.07.024_bib6","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1086\/383228","article-title":"Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2","volume":"74","author":"Li","year":"2004","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ymthe.2020.07.024_bib7","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1124\/dmd.109.028530","article-title":"Expression and characterization of CYP4V2 as a fatty acid \u03c9-hydroxylase","volume":"37","author":"Nakano","year":"2009","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.ymthe.2020.07.024_bib8","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1124\/mol.112.080085","article-title":"CYP4V2 in Bietti\u2019s crystalline dystrophy: ocular localization, metabolism of \u03c9-3-polyunsaturated fatty acids, and functional deficit of the p.H331P variant","volume":"82","author":"Nakano","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.ymthe.2020.07.024_bib9","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1167\/iovs.09-3665","article-title":"Alterations in serum fatty acid concentrations and desaturase activities in Bietti crystalline dystrophy unaffected by CYP4V2 genotypes","volume":"51","author":"Lai","year":"2010","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ymthe.2020.07.024_bib10","doi-asserted-by":"crossref","first-page":"5572","DOI":"10.1167\/iovs.13-13717","article-title":"Generation and characterization of a murine model of Bietti crystalline dystrophy","volume":"55","author":"Lockhart","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ymthe.2020.07.024_bib11","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.omtn.2017.09.009","article-title":"CRISPR\/Cas9 genome-editing system in human stem cells: current status and future prospects","volume":"9","author":"Zhang","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.ymthe.2020.07.024_bib12","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.stem.2008.10.015","article-title":"Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crx-deficient mice","volume":"4","author":"Lamba","year":"2009","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ymthe.2020.07.024_bib13","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0140-6736(14)61376-3","article-title":"Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt\u2019s macular dystrophy: follow-up of two open-label phase 1\/2 studies","volume":"385","author":"Schwartz","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.ymthe.2020.07.024_bib14","doi-asserted-by":"crossref","first-page":"3936","DOI":"10.1073\/pnas.1717338115","article-title":"Reduction of lipid accumulation rescues Bietti\u2019s crystalline dystrophy phenotypes","volume":"115","author":"Hata","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2020.07.024_bib15","first-page":"47","article-title":"Changes of serum lipids in patients with Bietti crystalline dystrophy","volume":"33","author":"Mengda","year":"2015","journal-title":"Chin. J. Exp. Ophthalmol."},{"key":"10.1016\/j.ymthe.2020.07.024_bib16","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s40259-017-0234-5","article-title":"Adeno-associated virus (AAV) as a vector for gene therapy","volume":"31","author":"Naso","year":"2017","journal-title":"BioDrugs"},{"key":"10.1016\/j.ymthe.2020.07.024_bib17","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.molmed.2015.12.007","article-title":"Cell-based therapy for degenerative retinal disease","volume":"22","author":"Zarbin","year":"2016","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.ymthe.2020.07.024_bib18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/ejhg.2016.184","article-title":"Identification and population history of CYP4V2 mutations in patients with Bietti crystalline corneoretinal dystrophy","volume":"25","author":"Jiao","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.ymthe.2020.07.024_bib19","first-page":"654","article-title":"Novel mutations in CYP4V2 in Bietti corneoretinal crystalline dystrophy: next-generation sequencing technology and genotype-phenotype correlations","volume":"25","author":"Meng","year":"2019","journal-title":"Mol. Vis."},{"key":"10.1016\/j.ymthe.2020.07.024_bib20","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/mgg3.109","article-title":"Novel insights into the molecular pathogenesis of CYP4V2-associated Bietti\u2019s retinal dystrophy","volume":"3","author":"Astuti","year":"2015","journal-title":"Mol. Genet. Genomic Med."},{"key":"10.1016\/j.ymthe.2020.07.024_bib21","first-page":"1806","article-title":"Identification of novel CYP4V2 gene mutations in 92 Chinese families with Bietti\u2019s crystalline corneoretinal dystrophy","volume":"20","author":"Meng","year":"2014","journal-title":"Mol. Vis."},{"key":"10.1016\/j.ymthe.2020.07.024_bib22","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.exer.2016.03.007","article-title":"Identification of CYP4V2 mutation in 36 Chinese families with Bietti crystalline corneoretinal dystrophy","volume":"146","author":"Yin","year":"2016","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.ymthe.2020.07.024_bib23","first-page":"738","article-title":"Novel mutations in the CYP4V2 gene associated with Bietti crystalline corneoretinal dystrophy","volume":"11","author":"Shan","year":"2005","journal-title":"Mol. Vis."},{"key":"10.1016\/j.ymthe.2020.07.024_bib24","doi-asserted-by":"crossref","first-page":"W252-8","DOI":"10.1093\/nar\/gku340","article-title":"SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information","volume":"42","author":"Biasini","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2020.07.024_bib25","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1182\/blood.V116.21.1589.1589","article-title":"Human IPS cells generated from adult peripheral blood cells and purified CD34+ cells by a non-integrating plasmid","volume":"116","author":"Huang","year":"2010","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2020.07.024_bib26","doi-asserted-by":"crossref","first-page":"e64496","DOI":"10.1371\/journal.pone.0064496","article-title":"Efficient generation of integration-free iPS cells from human adult peripheral blood using BCL-XL together with Yamanaka factors","volume":"8","author":"Su","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ymthe.2020.07.024_bib27","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"Ran","year":"2013","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.ymthe.2020.07.024_bib28","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1146\/annurev.neuro.24.1.1161","article-title":"Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations","volume":"24","author":"Meaney","year":"2001","journal-title":"Annu. Rev. Neurosci."},{"key":"10.1016\/j.ymthe.2020.07.024_bib29","doi-asserted-by":"crossref","first-page":"e1006780","DOI":"10.1371\/journal.pgen.1006780","article-title":"Genetic compensation: a phenomenon in search of mechanisms","volume":"13","author":"El-Brolosy","year":"2017","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ymthe.2020.07.024_bib30","first-page":"e1912","article-title":"BODIPY 493\/503 staining of neutral lipid droplets for microscopy and quantification by flow cytometry","volume":"6","author":"Qiu","year":"2016","journal-title":"Biol. Protoc."},{"key":"10.1016\/j.ymthe.2020.07.024_bib31","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1046\/j.1529-8817.2001.00130.x","article-title":"Liberation of 5,8,11,14,17-eicosapentaenoic acid and other polyunsaturated fatty acids from lipids as a grazer defense reaction in epilithic diatom biofilms","volume":"37","author":"J\u00fcttner","year":"2001","journal-title":"J.\u00a0Phycol."},{"key":"10.1016\/j.ymthe.2020.07.024_bib32","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/j.1365-2362.2008.01959.x","article-title":"Fat overload aggravates oxidative stress in patients with the metabolic syndrome","volume":"38","author":"Cardona","year":"2008","journal-title":"Eur. J. Clin. Invest."},{"key":"10.1016\/j.ymthe.2020.07.024_bib33","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1194\/jlr.E069880","article-title":"Lipotoxicity: many roads to cell dysfunction and cell death: introduction to a thematic review series","volume":"57","author":"Schaffer","year":"2016","journal-title":"J.\u00a0Lipid Res."},{"issue":"3C","key":"10.1016\/j.ymthe.2020.07.024_bib34","doi-asserted-by":"crossref","first-page":"14S","DOI":"10.1016\/0002-9343(91)90279-7","article-title":"Reactive oxygen species in living systems: source, biochemistry, and role in human disease","volume":"91","author":"Halliwell","year":"1991","journal-title":"Am. J. Med."},{"key":"10.1016\/j.ymthe.2020.07.024_bib35","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.stem.2009.07.002","article-title":"Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells","volume":"5","author":"Idelson","year":"2009","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ymthe.2020.07.024_bib36","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.stem.2013.07.001","article-title":"Genetic and epigenetic variations in iPSCs: potential causes and implications for application","volume":"13","author":"Liang","year":"2013","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ymthe.2020.07.024_bib37","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1136\/jmg.2004.029066","article-title":"Recessive mutations in the CYP4V2 gene in East Asian and Middle Eastern patients with Bietti crystalline corneoretinal dystrophy","volume":"42","author":"Lin","year":"2005","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.ymthe.2020.07.024_bib38","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ab.2012.10.022","article-title":"A highly efficient, high-throughput lipidomics platform for the quantitative detection of eicosanoids in human whole blood","volume":"433","author":"Song","year":"2013","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.ymthe.2020.07.024_bib39","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10545-010-9061-2","article-title":"A general introduction to the biochemistry of mitochondrial fatty acid \u03b2-oxidation","volume":"33","author":"Houten","year":"2010","journal-title":"J.\u00a0Inherit. Metab. Dis."},{"issue":"Suppl","key":"10.1016\/j.ymthe.2020.07.024_bib40","doi-asserted-by":"crossref","first-page":"S138","DOI":"10.1194\/jlr.R800079-JLR200","article-title":"Fatty acid metabolism: target for metabolic syndrome","volume":"50","author":"Wakil","year":"2009","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.ymthe.2020.07.024_bib41","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.2337\/diabetes.51.5.1477","article-title":"Increased efficiency of fatty acid uptake contributes to lipid accumulation in skeletal muscle of high fat-fed insulin-resistant rats","volume":"51","author":"Hegarty","year":"2002","journal-title":"Diabetes"},{"key":"10.1016\/j.ymthe.2020.07.024_bib42","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2020.07.024_bib43","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1016\/S0891-5849(02)01082-1","article-title":"Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells","volume":"33","author":"Weigel","year":"2002","journal-title":"Free Radic. Biol. Med."},{"issue":"Suppl 4","key":"10.1016\/j.ymthe.2020.07.024_bib44","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1038\/sj.ijo.0802854","article-title":"Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation","volume":"28","author":"Lelliott","year":"2004","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"10.1016\/j.ymthe.2020.07.024_bib45","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/acps.12265","article-title":"Effects of oxidative stress on fatty acid- and one-carbon-metabolism in psychiatric and cardiovascular disease comorbidity","volume":"130","author":"Assies","year":"2014","journal-title":"Acta Psychiatr. Scand."},{"key":"10.1016\/j.ymthe.2020.07.024_bib46","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S1734-1140(13)71005-3","article-title":"Oxidative stress, polyunsaturated fatty acids-derived oxidation products and bisretinoids as potential inducers of CNS diseases: focus on age-related macular degeneration","volume":"65","author":"Nowak","year":"2013","journal-title":"Pharmacol. Rep."},{"key":"10.1016\/j.ymthe.2020.07.024_bib47","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/BJ20110162","article-title":"Assessing mitochondrial dysfunction in cells","volume":"435","author":"Brand","year":"2011","journal-title":"Biochem. J."},{"key":"10.1016\/j.ymthe.2020.07.024_bib48","first-page":"191","article-title":"Apoptosis measurement by annexin V staining","volume":"88","author":"Miller","year":"2004","journal-title":"Methods Mol. Med."},{"key":"10.1016\/j.ymthe.2020.07.024_bib49","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.bbrc.2011.06.186","article-title":"Discrimination between primary necrosis and apoptosis by necrostatin-1 in annexin V-positive\/propidium iodide-negative cells","volume":"411","author":"Sawai","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ymthe.2020.07.024_bib50","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.apsb.2012.05.003","article-title":"The role of fatty acid metabolism and lipotoxicity in pancreatic \u03b2-cell injury: identification of potential therapeutic targets","volume":"2","author":"Yang","year":"2012","journal-title":"Acta Pharm. Sin. B"},{"issue":"Suppl 1","key":"10.1016\/j.ymthe.2020.07.024_bib51","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1038\/onc.2009.45","article-title":"PUMA, a potent killer with or without p53","volume":"27","author":"Yu","year":"2008","journal-title":"Oncogene"},{"key":"10.1016\/j.ymthe.2020.07.024_bib52","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1158\/1535-7163.895.3.8","article-title":"p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas","volume":"3","author":"Qin","year":"2004","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.ymthe.2020.07.024_bib53","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1161\/STROKEAHA.109.561852","article-title":"Neuroprotection against hypoxic-ischemic brain injury by inhibiting the apoptotic protease activating factor-1 pathway","volume":"41","author":"Gao","year":"2010","journal-title":"Stroke"},{"key":"10.1016\/j.ymthe.2020.07.024_bib54","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0005-2728(98)00109-1","article-title":"Mitochondrial control of apoptosis: the role of cytochrome c","volume":"1366","author":"Cai","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ymthe.2020.07.024_bib55","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s11745-001-0798-1","article-title":"Essential fatty acids in visual and brain development","volume":"36","author":"Uauy","year":"2001","journal-title":"Lipids"},{"key":"10.1016\/j.ymthe.2020.07.024_bib56","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s10495-008-0298-2","article-title":"Dietary polyunsaturated fatty acids as inducers of apoptosis: implications for cancer","volume":"14","author":"Serini","year":"2009","journal-title":"Apoptosis"},{"key":"10.1016\/j.ymthe.2020.07.024_bib57","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1046\/j.1471-4159.2003.01571.x","article-title":"Palmitic and stearic fatty acids induce caspase-dependent and -independent cell death in nerve growth factor differentiated PC12 cells","volume":"84","author":"Ulloth","year":"2003","journal-title":"J.\u00a0Neurochem."},{"key":"10.1016\/j.ymthe.2020.07.024_bib58","doi-asserted-by":"crossref","first-page":"11858","DOI":"10.18632\/oncotarget.24405","article-title":"Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review","volume":"9","author":"Moloudizargari","year":"2018","journal-title":"Oncotarget"},{"key":"10.1016\/j.ymthe.2020.07.024_bib59","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.stem.2013.05.016","article-title":"Modeling human disease with pluripotent stem cells: from genome association to function","volume":"12","author":"Merkle","year":"2013","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ymthe.2020.07.024_bib60","series-title":"Importance of fatty acids in physiopathology of human body. In Fatty Acids (IntechOpen)","first-page":"3","author":"Nagy","year":"2017"},{"key":"10.1016\/j.ymthe.2020.07.024_bib61","first-page":"3187","article-title":"Lipids of human retina, retinal pigment epithelium, and Bruch\u2019s membrane\/choroid: comparison of macular and peripheral regions","volume":"34","author":"G\u00fclcan","year":"1993","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ymthe.2020.07.024_bib62","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1146\/annurev.nutr.21.1.193","article-title":"Peroxisomal \u03b2-oxidation and peroxisome proliferator-activated receptor \u03b1: an adaptive metabolic system","volume":"21","author":"Reddy","year":"2001","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.ymthe.2020.07.024_bib63","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1016\/j.bcp.2008.03.004","article-title":"Cytochrome P450 omega hydroxylase (CYP4) function in fatty acid metabolism and metabolic diseases","volume":"75","author":"Hardwick","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ymthe.2020.07.024_bib64","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2217\/clp.09.85","article-title":"Mechanisms and clinical implications of hepatocyte lipoapoptosis","volume":"5","author":"Cazanave","year":"2010","journal-title":"Clin. Lipidol."},{"key":"10.1016\/j.ymthe.2020.07.024_bib65","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1001\/archophthalmol.2011.34","article-title":"Dietary \u03c9-3 fatty acid and fish intake and incident age-related macular degeneration in women","volume":"129","author":"Christen","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"10.1016\/j.ymthe.2020.07.024_bib66","doi-asserted-by":"crossref","first-page":"821","DOI":"10.2217\/clp.09.65","article-title":"Dual roles of polyunsaturated fatty acids in retinal physiology and pathophysiology associated with retinal degeneration","volume":"4","author":"Tanito","year":"2009","journal-title":"Clin. Lipidol."},{"key":"10.1016\/j.ymthe.2020.07.024_bib67","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1194\/jlr.R066597","article-title":"Oxidative stress and lipotoxicity","volume":"57","author":"Hauck","year":"2016","journal-title":"J.\u00a0Lipid Res."},{"key":"10.1016\/j.ymthe.2020.07.024_bib68","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1167\/iovs.14-14633","article-title":"Mitochondrial oxidative stress in the retinal pigment epithelium leads to localized retinal degeneration","volume":"55","author":"Mao","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ymthe.2020.07.024_bib69","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1146\/annurev.pharmtox.47.120505.105122","article-title":"Mitochondrial oxidative stress: implications for cell death","volume":"47","author":"Orrenius","year":"2007","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.ymthe.2020.07.024_bib70","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0928-4680(00)00053-5","article-title":"Oxidative stress and apoptosis","volume":"7","author":"Kannan","year":"2000","journal-title":"Pathophysiology"},{"key":"10.1016\/j.ymthe.2020.07.024_bib71","doi-asserted-by":"crossref","first-page":"e0116195","DOI":"10.1371\/journal.pone.0116195","article-title":"Comprehensive profiling of plasma fatty acid concentrations in young healthy Canadian adults","volume":"10","author":"Abdelmagid","year":"2015","journal-title":"PLoS ONE"},{"key":"10.1016\/j.ymthe.2020.07.024_bib72","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1146\/annurev.bi.52.070183.002541","article-title":"Fatty acid synthesis and its regulation","volume":"52","author":"Wakil","year":"1983","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.ymthe.2020.07.024_bib73","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1073\/pnas.0630588100","article-title":"Triglyceride accumulation protects against fatty acid-induced lipotoxicity","volume":"100","author":"Listenberger","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2020.07.024_bib74","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1167\/iovs.07-1601","article-title":"Development and characterization of an adult retinal explant organotypic tissue culture system as an in\u00a0vitro intraocular stem cell transplantation model","volume":"49","author":"Johnson","year":"2008","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ymthe.2020.07.024_bib75","doi-asserted-by":"crossref","first-page":"8047","DOI":"10.1016\/j.biomaterials.2012.07.033","article-title":"Generation of hESC-derived retinal pigment epithelium on biopolymer coated polyimide membranes","volume":"33","author":"Subrizi","year":"2012","journal-title":"Biomaterials"},{"key":"10.1016\/j.ymthe.2020.07.024_bib76","doi-asserted-by":"crossref","first-page":"22819","DOI":"10.18632\/oncotarget.8185","article-title":"Features specific to retinal pigment epithelium cells derived from three-dimensional human embryonic stem cell cultures\u2014a new donor for cell therapy","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.ymthe.2020.07.024_bib77","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.5966\/sctm.2014-0079","article-title":"ROCK inhibition extends passage of pluripotent stem cell-derived retinal pigmented epithelium","volume":"3","author":"Croze","year":"2014","journal-title":"Stem Cells Transl. Med."},{"key":"10.1016\/j.ymthe.2020.07.024_bib78","first-page":"2584","article-title":"TREK-TRAAK two-pore domain potassium channels protect human retinal pigment epithelium cells from oxidative stress","volume":"42","author":"Huang","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.ymthe.2020.07.024_bib79","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J.\u00a0Biol. Chem."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001620303750?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001620303750?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T17:59:20Z","timestamp":1761501560000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001620303750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":79,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["S1525001620303750"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2020.07.024","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2020,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"PSCs Reveal PUFA-Provoked Mitochondrial Stress as a Central Node Potentiating RPE Degeneration in Bietti\u2019s Crystalline Dystrophy","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2020.07.024","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Authors.","name":"copyright","label":"Copyright"}]}}