{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:54:56Z","timestamp":1791305696208,"version":"4.3.1"},"reference-count":66,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000310","name":"Retina UK","doi-asserted-by":"publisher","award":["GR594"],"award-info":[{"award-number":["GR594"]}],"id":[{"id":"10.13039\/501100000310","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017645","name":"Moorfields Eye Charity","doi-asserted-by":"publisher","award":["569249"],"award-info":[{"award-number":["569249"]}],"id":[{"id":"10.13039\/501100017645","id-type":"DOI","asserted-by":"publisher"}]},{"award":["569249"],"award-info":[{"award-number":["569249"]}],"id":[{"id":"https:\/\/ror.org\/017hm5p20","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205174\/Z\/16\/Z"],"award-info":[{"award-number":["205174\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"award":["205174\/Z\/16\/Z"],"award-info":[{"award-number":["205174\/Z\/16\/Z"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>NADPH-dependent retinol dehydrogenase 12 (RDH12) reduces all-trans-retinal in photoreceptor inner segments to regulate the phototransduction cascade and control the concentration of retinoids in the retina. Variants in RDH12 have been reported to cause an array of retinal disease phenotypes, including autosomal recessive (AR) Leber congenital amaurosis (LCA), a severe form of childhood blindness, and autosomal dominant (AD) retinitis pigmentosa (RP), a milder late-onset rod-dominant disease. Animal models have failed to recapitulate the clinical phenotype; hence, we generated human induced pluripotent stem cell (hiPSC) derived retinal organoids (RO) from a patient with homozygous missense variant c.619A&gt;G p.(Asn207Asp) in RDH12 (RDH12-AR), a patient with heterozygous c.759del p.(Phe254Leufs*24) (RDH12-AD), and an unaffected control. RDH12-AR ROs develop shortened rod and cone photoreceptors (from the outer limiting membrane to the tip of the outer segment), which lack RDH12 localisation in the inner segment. Bulk transcriptomic analysis revealed cone marker and apoptosis dysregulation in RDH12-AR ROs compared to unaffected controls, but phospholipid transport is perturbed in RDH12-AR ROs compared to RDH12-AD. Our study helps to decipher the distinct disease pathways involved in RDH12 retinopathies; however, further modelling from additional patients with isogenic controls will strengthen the findings and aid identification of targets for therapeutic approaches.<\/jats:p>","DOI":"10.3390\/ijms27198880","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:21:46Z","timestamp":1791303706000},"page":"8880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autosomal Recessive RDH12-Leber Congenital Amaurosis Retinal Organoids Suggest Phospholipid Pathway Dysregulation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2532-4004","authenticated-orcid":false,"given":"C\u00e9cile","family":"M\u00e9j\u00e9case","sequence":"first","affiliation":[{"name":"Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK"},{"name":"Ocular Genomics and Therapeutics, The Francis Crick Institute, London NW1 1AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Lyes","family":"Toualbi","sequence":"additional","affiliation":[{"name":"Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK"},{"name":"Ocular Genomics and Therapeutics, The Francis Crick Institute, London NW1 1AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3921-3367","authenticated-orcid":false,"given":"Ya","family":"Zhou","sequence":"additional","affiliation":[{"name":"Electron Microscopy Science Technology Platform, The Francis Crick Institute, London NW1 1AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6871-9498","authenticated-orcid":false,"given":"Riccardo","family":"Cheloni","sequence":"additional","affiliation":[{"name":"Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK"},{"name":"Department of Genetics, Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Neelima","family":"Nair","sequence":"additional","affiliation":[{"name":"Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5598-6274","authenticated-orcid":false,"given":"Nicholas","family":"Owen","sequence":"additional","affiliation":[{"name":"Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Hajrah","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK"},{"name":"Ocular Genomics and Therapeutics, The Francis Crick Institute, London NW1 1AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Jieren","family":"Bornia","sequence":"additional","affiliation":[{"name":"Ocular Genomics and Therapeutics, The Francis Crick Institute, London NW1 1AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Maria","family":"Toms","sequence":"additional","affiliation":[{"name":"Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK"},{"name":"Ocular Genomics and Therapeutics, The Francis Crick Institute, London NW1 1AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4509-6109","authenticated-orcid":false,"given":"Pablo","family":"Soro-Barrio","sequence":"additional","affiliation":[{"name":"Bioinformatics and Biostatistics Science Technology Platform, The Francis Crick Institute, London NW1 1AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-5360","authenticated-orcid":false,"given":"Mariya","family":"Moosajee","sequence":"additional","affiliation":[{"name":"Development, Ageing and Disease, UCL Institute of Ophthalmology, London EC1V 9EL, UK"},{"name":"Ocular Genomics and Therapeutics, The Francis Crick Institute, London NW1 1AT, UK"},{"name":"Department of Genetics, Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"107793","DOI":"10.1016\/j.exer.2019.107793","article-title":"Retinol dehydrogenase 12 (RDH12): Role in vision, retinal disease and future perspectives","volume":"188","author":"Sarkar","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_3","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."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sajovic, J., Megli\u010d, A., Glava\u010d, D., Markelj, \u0160., Hawlina, M., and Fakin, A. (2022). The Role of Vitamin A in Retinal Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031014"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1097\/IAE.0000000000002242","article-title":"Phenotypic variability of recessive RDH12-associated retinal dystrophy","volume":"39","author":"Zou","year":"2019","journal-title":"Retina"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1080\/13816810.2020.1802763","article-title":"Macula-predominant retinopathy associated with biallelic variants in RDH12","volume":"41","author":"Arno","year":"2020","journal-title":"Ophthalmic Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1001\/archopht.126.9.1301","article-title":"Association of a novel mutation in the retinol dehydrogenase 12 (RDH12) gene with autosomal dominant retinitis pigmentosa","volume":"126","author":"Fingert","year":"2008","journal-title":"Arch. Ophthalmol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1136\/bjophthalmol-2020-318034","article-title":"Novel disease-causing variant in RDH12 presenting with autosomal dominant retinitis pigmentosa","volume":"106","author":"Muthiah","year":"2022","journal-title":"Br. J. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sarkar, H., Dubis, A.M., Downes, S., and Moosajee, M. (2020). Novel Heterozygous Deletion in Retinol Dehydrogenase 12 (RDH12) Causes Familial Autosomal Dominant Retinitis Pigmentosa. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00335"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1080\/13816810.2022.2062392","article-title":"RDH12 retinopathy: Clinical features, biology, genetics and future directions","volume":"43","author":"Michaelides","year":"2022","journal-title":"Ophthalmic Genet."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sarkar, H., Toms, M., and Moosajee, M. (2021). Involvement of Oxidative and Endoplasmic Reticulum Stress in RDH12-Related Retinopathies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168863"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1128\/MCB.01486-06","article-title":"Targeted disruption of the murine retinal dehydrogenase gene Rdh12 does not limit visual cycle function","volume":"27","author":"Kurth","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"M\u00e9j\u00e9case, C., Zhou, Y., Owen, N., Soro-Barrio, P., Cheloni, R., Nair, N., Sarkar, H., Toualbi, L., and Moosajee, M. (2025). Dominant RDH12-retinitis pigmentosa impairs photoreceptor development and implicates cone involvement in retinal organoids. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1511066"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"102449","DOI":"10.1016\/j.scr.2021.102449","article-title":"Generation of two human iPSC lines from patients with autosomal dominant retinitis pigmentosa (UCLi014-A) and autosomal recessive Leber congenital amaurosis (UCLi015-A), associated with RDH12 variants","volume":"54","author":"Sarkar","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_15","first-page":"1789","article-title":"Detailed clinical characterisation, unique features and natural history of autosomal recessive RDH12-associated retinal degeneration","volume":"103","author":"Fahim","year":"2019","journal-title":"Br. J. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/S0891-5849(01)00495-6","article-title":"Retinoic acid reduces apoptosis and oxidative stress by preservation of SOD protein level","volume":"30","author":"Ahlemeyer","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3476","DOI":"10.1364\/BOE.455783","article-title":"In situ autofluorescence lifetime assay of a photoreceptor stimulus response in mouse retina and human retinal organoids","volume":"13","author":"Samimi","year":"2022","journal-title":"Biomed. Opt. Express"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.stemcr.2022.12.002","article-title":"Comprehensive characterization of fetal and mature retinal cell identity to assess the fidelity of retinal organoids","volume":"18","author":"Kim","year":"2023","journal-title":"Stem Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41580-023-00604-z","article-title":"Regulation of phospholipid distribution in the lipid bilayer by flippases and scramblases","volume":"24","author":"Sakuragi","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"bio036632","DOI":"10.1242\/bio.036632","article-title":"Characterisation of maturation of photoreceptor cell subtypes during zebrafish retinal development","volume":"7","author":"Crespo","year":"2018","journal-title":"Biol. Open"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.ajo.2012.05.007","article-title":"Histologic Development of the Human Fovea From Midgestation to Maturity","volume":"154","author":"Hendrickson","year":"2012","journal-title":"Am. J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/(SICI)1097-0185(199809)252:1<133::AID-AR11>3.0.CO;2-P","article-title":"Photoreceptor morphogenesis in the human retina: A scanning electron microscopic study","volume":"252","author":"Narayanan","year":"1998","journal-title":"Anat. Rec."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.tcb.2020.08.005","article-title":"Photoreceptor Discs: Built Like Ectosomes","volume":"30","author":"Spencer","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"BIO255","DOI":"10.1167\/iovs.17-21868","article-title":"Photoreceptor-Based Biomarkers in AOSLO Retinal Imaging","volume":"58","author":"Litts","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1167\/iovs.65.3.9","article-title":"Adaptive Optics Retinal Imaging in RDH12-associated Early Onset Severe Retinal Dystrophy","volume":"65","author":"Dixit","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101787","DOI":"10.1016\/j.redox.2020.101787","article-title":"Evidence of complement dysregulation in outer retina of Stargardt disease donor eyes","volume":"37","author":"Hu","year":"2020","journal-title":"Redox Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Katchalski-Katzir, E., Kasher, R., and Fridkin, M. (2006). Amino Acids: Physicochemical Properties. Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine, Springer.","DOI":"10.1007\/3-540-29623-9_2260"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6958","DOI":"10.1074\/jbc.RA120.013189","article-title":"Activation of JNK signaling promotes all-trans-retinal\u2013induced photoreceptor apoptosis in mice","volume":"295","author":"Liao","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"104686","DOI":"10.1016\/j.jbc.2023.104686","article-title":"eIF2\u03b1 incites photoreceptor cell and retina damage by all-trans-retinal","volume":"299","author":"He","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_30","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."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19565","DOI":"10.1073\/pnas.0707477104","article-title":"Redundant and unique roles of retinol dehydrogenases in the mouse retina","volume":"104","author":"Maeda","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.preteyeres.2014.09.001","article-title":"Congenital stationary night blindness: An analysis and update of genotype\u2013phenotype correlations and pathogenic mechanisms","volume":"45","author":"Zeitz","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.oret.2023.09.007","article-title":"Clinical and Genetic Characterization of RDH12-Retinal Dystrophy in a South American Cohort","volume":"8","author":"Moya","year":"2024","journal-title":"Ophthalmol. Retin."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5225","DOI":"10.1167\/iovs.18-24708","article-title":"RDH12 Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function","volume":"59","author":"Aleman","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1167\/iovs.06-1521","article-title":"CNGB3 Achromatopsia with Progressive Loss of Residual Cone Function and Impaired Rod-Mediated Function","volume":"48","author":"Khan","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1016\/j.ajhg.2021.06.003","article-title":"Unique variants in CLCN3, encoding an endosomal anion\/proton exchanger, underlie a spectrum of neurodevelopmental disorders","volume":"108","author":"Duncan","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.exer.2019.04.014","article-title":"Pregabalin affords retinal neuroprotection in diabetic rats: Suppression of retinal glutamate, microglia cell expression and apoptotic cell death","volume":"184","author":"Ali","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_38","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":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100042","DOI":"10.1194\/jlr.TR120000742","article-title":"Bisretinoid phospholipid and vitamin A aldehyde: Shining a light","volume":"62","author":"Kim","year":"2021","journal-title":"J. Lipid Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"101037","DOI":"10.1016\/j.preteyeres.2021.101037","article-title":"Dynamic lipid turnover in photoreceptors and retinal pigment epithelium throughout life","volume":"89","author":"Lewandowski","year":"2022","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"37697","DOI":"10.1074\/jbc.M608375200","article-title":"Retinol Dehydrogenase (RDH12) Protects Photoreceptors from Light-induced Degeneration in Mice","volume":"281","author":"Maeda","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7035","DOI":"10.1021\/bi050226k","article-title":"Biochemical properties of purified human retinol dehydrogenase 12 (RDH12): Catalytic efficiency toward retinoids and C9 aldehydes and effects of cellular retinol-binding protein type I (CRBPI) and cellular retinaldehyde-binding protein (CRALBP) on the oxidation and reduction of retinoids","volume":"44","author":"Belyaeva","year":"2005","journal-title":"Biochemistry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.bbadis.2008.03.004","article-title":"Effect of lipid peroxidation products on the activity of human retinol dehydrogenase 12 (RDH12) and retinoid metabolism","volume":"1782","author":"Lee","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"183382","DOI":"10.1016\/j.bbamem.2020.183382","article-title":"Physiological roles of transverse lipid asymmetry of animal membranes","volume":"1862","author":"Clarke","year":"2020","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Biomembr."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.molmed.2022.11.001","article-title":"ABC transporters: Human disease and pharmacotherapeutic potential","volume":"29","author":"Moore","year":"2023","journal-title":"Trends Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e45100","DOI":"10.7554\/eLife.45100","article-title":"Impaired ABCA1\/ABCG1-mediated lipid efflux in the mouse retinal pigment epithelium (RPE) leads to retinal degeneration","volume":"8","author":"Storti","year":"2019","journal-title":"eLife"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Katzeff, J.S., Lok, H.C., Bhatia, S., Fu, Y., Halliday, G.M., and Kim, W.S. (2022). ATP-binding cassette transporter expression is widely dysregulated in frontotemporal dementia with TDP-43 inclusions. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.1043127"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1042\/BST20150105","article-title":"Understanding the function of ABCA7 in Alzheimer\u2019s disease","volume":"43","author":"Li","year":"2015","journal-title":"Biochem. Soc. Trans."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.15252\/emmm.201505298","article-title":"Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration","volume":"7","author":"Zhao","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0163-7827(94)00004-6","article-title":"Lipid studies in retinitis pigmentosa","volume":"34","author":"McColl","year":"1995","journal-title":"Prog. Lipid Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6505","DOI":"10.1007\/s00018-021-03917-4","article-title":"A look into retinal organoids: Methods, analytical techniques, and applications","volume":"78","author":"Afanasyeva","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101781","DOI":"10.1016\/j.redox.2020.101781","article-title":"Complement activation, lipid metabolism, and mitochondrial injury: Converging pathways in age-related macular degeneration","volume":"37","author":"Tan","year":"2020","journal-title":"Redox Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Singh, R.K., and Nasonkin, I.O. (2020). Limitations and Promise of Retinal Tissue From Human Pluripotent Stem Cells for Developing Therapies of Blindness. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00179"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"108269","DOI":"10.1016\/j.visres.2023.108269","article-title":"Utilization of the retinal organoid model to evaluate the feasibility of genetic strategies to ameliorate retinal disease(s)","volume":"210","author":"Kelley","year":"2023","journal-title":"Vis. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Linkens, K., M\u00e9j\u00e9case, C., and Moosajee, M. (2025). Differentiation of Retinal Pigment Epithelium (RPE) and Retinal Organoids from Human iPSCs. Methods in Molecular Biology, Springer.","DOI":"10.1007\/7651_2025_674"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1002\/stem.2586","article-title":"Generation of Storable Retinal Organoids and Retinal Pigmented Epithelium from Adherent Human iPS Cells in Xeno-Free and Feeder-Free Conditions","volume":"35","author":"Reichman","year":"2017","journal-title":"Stem Cells"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.stemcr.2017.07.022","article-title":"Recapitulation of Human Retinal Development from Human Pluripotent Stem Cells Generates Transplantable Populations of Cone Photoreceptors","volume":"9","author":"Kruczek","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"102113","DOI":"10.1016\/j.scr.2020.102113","article-title":"Generation of two human control iPS cell lines (UCLi016-A and UCLi017-A) from healthy donors with no known ocular conditions","volume":"49","author":"Harding","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8518","DOI":"10.1073\/pnas.1324212111","article-title":"From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium","volume":"111","author":"Reichman","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet J."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_64","unstructured":"R Development Core Team (2008). R a Language and Environment for Statistical Computing: Reference Index, R Foundation for Statistical Computing."},{"key":"ref_65","first-page":"D498","article-title":"The reactome pathway knowledgebase","volume":"48","author":"Jassal","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"D419","DOI":"10.1093\/nar\/gky1038","article-title":"PANTHER version 14: More genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools","volume":"47","author":"Mi","year":"2019","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8880\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:22:00Z","timestamp":1791303720000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":66,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198880"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198880","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]}}}