{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:18:52Z","timestamp":1790705932744,"version":"4.1.0"},"reference-count":125,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T00:00:00Z","timestamp":1679961600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["Z01EY000546"],"award-info":[{"award-number":["Z01EY000546"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["Z01EY000450"],"award-info":[{"award-number":["Z01EY000450"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["ZIATR000018-06"],"award-info":[{"award-number":["ZIATR000018-06"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,3,23]]},"abstract":"<jats:p>\n                    Ciliopathies manifest from sensory abnormalities to syndromic disorders with multi-organ pathologies, with retinal degeneration a highly penetrant phenotype. Photoreceptor cell death is a major cause of incurable blindness in retinal ciliopathies. To identify drug candidates to maintain photoreceptor survival, we performed an unbiased, high-throughput screening of over 6000 bioactive small molecules using retinal organoids differentiated from induced pluripotent stem cells (iPSC) of\n                    <jats:italic>rd16<\/jats:italic>\n                    mouse, which is a model of Leber congenital amaurosis (LCA) type 10 caused by mutations in the cilia-centrosomal gene\n                    <jats:italic>CEP290<\/jats:italic>\n                    . We identified five non-toxic positive hits, including the lead molecule reserpine, which maintained photoreceptor development and survival in\n                    <jats:italic>rd16<\/jats:italic>\n                    organoids. Reserpine also improved photoreceptors in retinal organoids derived from induced pluripotent stem cells of\n                    <jats:italic>LCA10<\/jats:italic>\n                    patients and in\n                    <jats:italic>rd16<\/jats:italic>\n                    mouse retina in vivo. Reserpine-treated patient organoids revealed modulation of signaling pathways related to cell survival\/death, metabolism, and proteostasis. Further investigation uncovered dysregulation of autophagy associated with compromised primary cilium biogenesis in patient organoids and\n                    <jats:italic>rd16<\/jats:italic>\n                    mouse retina. Reserpine partially restored the balance between autophagy and the ubiquitin-proteasome system at least in part by increasing the cargo adaptor p62, resulting in improved primary cilium assembly. Our study identifies effective drug candidates in preclinical studies of\n                    <jats:italic>CEP290<\/jats:italic>\n                    retinal ciliopathies through cross-species drug discovery using iPSC-derived organoids, highlights the impact of proteostasis in the pathogenesis of ciliopathies, and provides new insights for treatments of retinal neurodegeneration.\n                  <\/jats:p>","DOI":"10.7554\/elife.83205","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T08:01:57Z","timestamp":1679990517000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.83205","source":"Crossref","is-referenced-by-count":38,"title":["Reserpine maintains photoreceptor survival in retinal ciliopathy by resolving proteostasis imbalance and ciliogenesis defects"],"prefix":"10.7554","volume":"12","author":[{"given":"Holly Y","family":"Chen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}],"name":"Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manju","family":"Swaroop","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"publisher"}],"name":"National Therapeutics for Rare and Neglected Diseases, National Center for Advancing Translational Sciences, National Institutes of Health","place":["Rockville, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9417-6215","authenticated-orcid":true,"given":"Samantha","family":"Papal","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}],"name":"Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam K","family":"Mondal","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}],"name":"Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3500-2984","authenticated-orcid":true,"given":"Hyun Beom","family":"Song","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}],"name":"Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Campello","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}],"name":"Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J","family":"Tawa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"publisher"}],"name":"National Therapeutics for Rare and Neglected Diseases, National Center for Advancing Translational Sciences, National Institutes of Health","place":["Rockville, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2716-1584","authenticated-orcid":true,"given":"Florian","family":"Regent","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}],"name":"Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Shimada","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}],"name":"Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunio","family":"Nagashima","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03v6m3209","id-type":"ROR","asserted-by":"publisher"}],"name":"Electron Microscopy Laboratory, National Cancer Institute, Center for Cancer Research, Leidos Biomedical Research, Frederick National Laboratory","place":["Frederick, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"de Val","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03v6m3209","id-type":"ROR","asserted-by":"publisher"}],"name":"Electron Microscopy Laboratory, National Cancer Institute, Center for Cancer Research, Leidos Biomedical Research, Frederick National Laboratory","place":["Frederick, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel G","family":"Jacobson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania","place":["Philadelphia, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1034-0757","authenticated-orcid":true,"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04pw6fb54","id-type":"ROR","asserted-by":"publisher"}],"name":"National Therapeutics for Rare and Neglected Diseases, National Center for Advancing Translational Sciences, National Institutes of Health","place":["Rockville, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1975-1141","authenticated-orcid":true,"given":"Anand","family":"Swaroop","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}],"name":"Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health","place":["Bethesda, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"3890","DOI":"10.1073\/pnas.0508214103","article-title":"Targeting of GFP to newborn rods by NRL promoter and temporal expression profiling of flow-sorted photoreceptors","volume":"103","author":"Akimoto","year":"2006","journal-title":"PNAS"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1001\/archneurpsyc.1956.02330260084008","article-title":"The effects of reserpine on schizophrenic patients","volume":"76","author":"Armitage","year":"1956","journal-title":"A.M.A. Archives of Neurology and Psychiatry"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"2185","DOI":"10.1093\/hmg\/ddu738","article-title":"Nephrocystin proteins NPHP5 and CEP290 regulate BBSome integrity, ciliary trafficking and cargo delivery","volume":"24","author":"Barbelanne","year":"2015","journal-title":"Human Molecular Genetics"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.1038\/srep11319","article-title":"A cost-effective and efficient reprogramming platform for large-scale production of integration-free human induced pluripotent stem cells in chemically defined culture","volume":"5","author":"Beers","year":"2015","journal-title":"Scientific Reports"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd5524","article-title":"Drug repurposing: misconceptions, challenges, and opportunities for academic researchers","volume":"13","author":"Begley","year":"2021","journal-title":"Science Translational Medicine"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1146\/annurev-vision-121219-081855","article-title":"Human organoids for the study of retinal development and disease","volume":"6","author":"Bell","year":"2020","journal-title":"Annual Review of Vision Science"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.neuint.2013.12.003","article-title":"The vesicular monoamine transporter 2: an underexplored pharmacological target","volume":"73","author":"Bernstein","year":"2014","journal-title":"Neurochemistry International"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: a cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194423","article-title":"Quantifying autophagy using novel LC3B and p62 TR-FRET assays","volume":"13","author":"Bresciani","year":"2018","journal-title":"PLOS ONE"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/gt.2014.39","article-title":"Cep290 gene transfer rescues Leber congenital amaurosis cellular phenotype","volume":"21","author":"Burnight","year":"2014","journal-title":"Gene Therapy"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"474","DOI":"10.3928\/23258160-20160419-12","article-title":"Reduction of diabetic macular edema in the untreated fellow eye following intravitreal injection of aflibercept","volume":"47","author":"Calvo","year":"2016","journal-title":"Ophthalmic Surgery, Lasers & Imaging Retina"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.1242\/dev.171686","article-title":"Reproducibility and staging of 3D human retinal organoids across multiple pluripotent stem cell lines","volume":"146","author":"Capowski","year":"2019","journal-title":"Development"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1093\/hmg\/ddl107","article-title":"In-Frame deletion in a novel centrosomal\/ciliary protein CEP290\/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse","volume":"15","author":"Chang","year":"2006","journal-title":"Human Molecular Genetics"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.763831","article-title":"The role of HDAC6 in autophagy and NLRP3 inflammasome","volume":"12","author":"Chang","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"bib15","first-page":"1077","article-title":"Three-Dimensional retinal organoids from mouse pluripotent stem cells mimic in vivo development with enhanced stratification and rod photoreceptor differentiation","volume":"22","author":"Chen","year":"2016","journal-title":"Molecular Vision"},{"key":"bib16","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aag0245","article-title":"Synergistically acting agonists and antagonists of G protein-coupled receptors prevent photoreceptor cell degeneration","volume":"9","author":"Chen","year":"2016","journal-title":"Science Signaling"},{"key":"bib17","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2020.100018","article-title":"HIPRO: a high-efficiency, hypoxia-induced protocol for generation of photoreceptors in retinal organoids from mouse pluripotent stem cells","volume":"1","author":"Chen","year":"2020","journal-title":"STAR Protocols"},{"key":"bib18","volume-title":"Reserpine","author":"Cheung","year":"2023"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1002\/humu.20565","article-title":"Centrosomal-ciliary gene CEP290\/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis","volume":"28","author":"Cideciyan","year":"2007","journal-title":"Human Mutation"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1093\/hmg\/ddr022","article-title":"Cone photoreceptors are the main targets for gene therapy of NPHP5 (IQCB1) or NPHP6 (CEP290) blindness: generation of an all-cone Nphp6 hypomorph mouse that mimics the human retinal ciliopathy","volume":"20","author":"Cideciyan","year":"2011","journal-title":"Human Molecular Genetics"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2012.3","article-title":"Antisense oligonucleotide (AON) -based therapy for Leber congenital amaurosis caused by a frequent mutation in CEP290","volume":"1","author":"Collin","year":"2012","journal-title":"Molecular Therapy - Nucleic Acids"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1002\/humu.21337","article-title":"Cep290, a gene with many faces: mutation overview and presentation of cep290base","volume":"31","author":"Coppieters","year":"2010","journal-title":"Human Mutation"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1016\/j.cell.2020.08.013","article-title":"Cell types of the human retina and its organoids at single-cell resolution","volume":"182","author":"Cowan","year":"2020","journal-title":"Cell"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1083\/jcb.201006105","article-title":"CEP290 tethers flagellar transition zone microtubules to the membrane and regulates flagellar protein content","volume":"190","author":"Craige","year":"2010","journal-title":"The Journal of Cell Biology"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.3390\/genes9040215","article-title":"Special issue introduction: inherited retinal disease: novel candidate genes, genotype-phenotype correlations, and inheritance models","volume":"9","author":"Cremers","year":"2018","journal-title":"Genes"},{"key":"bib26","first-page":"1442","article-title":"The influence of reserpine and propranolol upon the IOP response to vanadate in the rabbit","volume":"26","author":"Delamere","year":"1985","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1086\/507318","article-title":"Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis","volume":"79","author":"den Hollander","year":"2006","journal-title":"American Journal of Human Genetics"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.preteyeres.2008.05.003","article-title":"Leber congenital amaurosis: genes, proteins and disease mechanisms","volume":"27","author":"den Hollander","year":"2008","journal-title":"Progress in Retinal and Eye Research"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.stemcr.2017.11.001","article-title":"Accelerated and improved differentiation of retinal organoids from pluripotent stem cells in rotating-wall vessel bioreactors","volume":"10","author":"DiStefano","year":"2018","journal-title":"Stem Cell Reports"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.omtn.2018.05.014","article-title":"Spliceosome-Mediated pre-mRNA trans-splicing can repair CEP290 mRNA","volume":"12","author":"Dooley","year":"2018","journal-title":"Molecular Therapy - Nucleic Acids"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"4525","DOI":"10.1172\/JCI69448","article-title":"Disruption of CEP290 microtubule\/membrane-binding domains causes retinal degeneration","volume":"123","author":"Drivas","year":"2013","journal-title":"The Journal of Clinical Investigation"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa5370","article-title":"Basal exon skipping and genetic pleiotropy: a predictive model of disease pathogenesis","volume":"7","author":"Drivas","year":"2015","journal-title":"Science Translational Medicine"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1016\/j.omtn.2018.07.010","article-title":"Splice-modulating oligonucleotide QR-110 restores CEP290 mRNA and function in human c.2991+1655A > G LCA10 models","volume":"12","author":"Dulla","year":"2018","journal-title":"Molecular Therapy - Nucleic Acids"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.stem.2013.05.011","article-title":"Integrating human pluripotent stem cells into drug development","volume":"12","author":"Engle","year":"2013","journal-title":"Cell Stem Cell"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.3390\/genes10080557","article-title":"Balancing the photoreceptor proteome: proteostasis network therapeutics for inherited retinal disease","volume":"10","author":"Faber","year":"2019","journal-title":"Genes"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"R2","DOI":"10.1093\/hmg\/ddx185","article-title":"Toward an elucidation of the molecular genetics of inherited retinal degenerations","volume":"26","author":"Farrar","year":"2017","journal-title":"Human Molecular Genetics"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1007\/s10571-014-0149-3","article-title":"Primary cilia in rat mature M\u00fcller glia: downregulation of IFT20 expression reduces sonic Hedgehog-mediated proliferation and dedifferentiation potential of M\u00fcller glia primary cultures","volume":"35","author":"Ferraro","year":"2015","journal-title":"Cellular and Molecular Neurobiology"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/nrd.2017.22","article-title":"Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles","volume":"16","author":"Galluzzi","year":"2017","journal-title":"Nature Reviews. Drug Discovery"},{"key":"bib39","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.100827","article-title":"Progress in treating inherited retinal diseases: early subretinal gene therapy clinical trials and candidates for future initiatives","volume":"77","author":"Garafalo","year":"2020","journal-title":"Progress in Retinal and Eye Research"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.ymthe.2019.08.013","article-title":"Long-Term structural outcomes of late-stage RPE65 gene therapy","volume":"28","author":"Gardiner","year":"2020","journal-title":"Molecular Therapy"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2012.21","article-title":"AON-mediated exon skipping restores ciliation in fibroblasts harboring the common Leber congenital amaurosis CEP290 mutation","volume":"1","author":"Gerard","year":"2012","journal-title":"Molecular Therapy - Nucleic Acids"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"2710","DOI":"10.1073\/pnas.1913179117","article-title":"Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases","volume":"117","author":"Hanany","year":"2020","journal-title":"PNAS"},{"key":"bib43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009259","article-title":"Loss of endocytosis-associated rabgef1 causes aberrant morphogenesis and altered autophagy in photoreceptors leading to retinal degeneration","volume":"16","author":"Hargrove-Grimes","year":"2020","journal-title":"PLOS Genetics"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","article-title":"Regulation mechanisms and signaling pathways of autophagy","volume":"43","author":"He","year":"2009","journal-title":"Annual Review of Genetics"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/nrd.2016.175","article-title":"Screening out irrelevant cell-based models of disease","volume":"15","author":"Horvath","year":"2016","journal-title":"Nature Reviews. Drug Discovery"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1113\/jphysiol.1960.sp006377","article-title":"Preganglionic sympathetic activity in normal and in reserpine-treated cats","volume":"150","author":"Iggo","year":"1960","journal-title":"The Journal of Physiology"},{"key":"bib47","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a033951","article-title":"Functional modules of the proteostasis network","volume":"12","author":"Jayaraj","year":"2020","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"bib48","first-page":"344","article-title":"A new combination of hypotensive drugs (reserpine, dihydralazine, furosemide and triamterene) for the treatment of arterial hypertension without risk of hypopotassaemia","volume":"11","author":"Kalliom\u00e4ki","year":"1969","journal-title":"Current Therapeutic Research, Clinical and Experimental"},{"key":"bib49","first-page":"663","article-title":"Transcriptome-Based molecular staging of human stem cell-derived retinal organoids uncovers accelerated photoreceptor differentiation by 9-cis retinal","volume":"25","author":"Kaya","year":"2019","journal-title":"Molecular Vision"},{"key":"bib50","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2020.100033","article-title":"Accelerated development of rod photoreceptors in retinal organoids derived from human pluripotent stem cells by supplementation with 9-cis retinal","volume":"1","author":"Kelley","year":"2020","journal-title":"STAR Protocols"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1172\/JCI73939","article-title":"Mtor: a pharmacologic target for autophagy regulation","volume":"125","author":"Kim","year":"2015","journal-title":"The Journal of Clinical Investigation"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.1016\/j.celrep.2016.10.074","article-title":"NRL-regulated transcriptome dynamics of developing rod photoreceptors","volume":"17","author":"Kim","year":"2016","journal-title":"Cell Reports"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"3642","DOI":"10.1172\/JCI99232","article-title":"Eupatilin rescues ciliary transition zone defects to ameliorate ciliopathy-related phenotypes","volume":"128","author":"Kim","year":"2018","journal-title":"The Journal of Clinical Investigation"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1083\/jcb.201709072","article-title":"Pathways of cellular proteostasis in aging and disease","volume":"217","author":"Klaips","year":"2018","journal-title":"The Journal of Cell Biology"},{"key":"bib55","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2020.100137","article-title":"A high-content screen for mucin-1-reducing compounds identifies fostamatinib as a candidate for rapid repurposing for acute lung injury","volume":"1","author":"Kost-Alimova","year":"2020","journal-title":"Cell Reports. Medicine"},{"key":"bib56","first-page":"331","article-title":"Accumulation of membranes and photoreceptor degeneration in mouse retina","volume":"57","author":"Kralj","year":"1998","journal-title":"Folia Morphologica"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1002\/stem.3239","article-title":"Pluripotent stem cell-derived retinal organoids for disease modeling and development of therapies","volume":"38","author":"Kruczek","year":"2020","journal-title":"Stem Cells"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/nrm4007","article-title":"P53 in survival, death and metabolic health: a lifeguard with a licence to kill","volume":"16","author":"Kruiswijk","year":"2015","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.793328","article-title":"Selective autophagy receptor p62\/SQSTM1, a pivotal player in stress and aging","volume":"10","author":"Kumar","year":"2022","journal-title":"Frontiers in Cell and Developmental Biology"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/emboj.2009.405","article-title":"HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy","volume":"29","author":"Lee","year":"2010","journal-title":"The EMBO Journal"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.bbrc.2015.04.145","article-title":"The anti-hypertensive drug reserpine induces neuronal cell death through inhibition of autophagic flux","volume":"462","author":"Lee","year":"2015","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1097\/IAE.0000000000003133","article-title":"Leber congenital amaurosis due to CEP290 mutations-severe vision impairment with a high unmet medical need: a review","volume":"41","author":"Leroy","year":"2021","journal-title":"Retina"},{"key":"bib63","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-016-0031-z","article-title":"P62 links the autophagy pathway and the ubiqutin-proteasome system upon ubiquitinated protein degradation","volume":"21","author":"Liu","year":"2016","journal-title":"Cellular & Molecular Biology Letters"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.trecan.2020.10.005","article-title":"Life and death decision-making by p53 and implications for cancer immunotherapy","volume":"7","author":"Liu","year":"2021","journal-title":"Trends in Cancer"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrneurol.2012.227","article-title":"The retina as a window to the brain-from eye research to CNS disorders","volume":"9","author":"London","year":"2013","journal-title":"Nature Reviews. Neurology"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"15917","DOI":"10.1073\/pnas.0704140104","article-title":"Hypomorphic CEP290\/NPHP6 mutations result in anosmia caused by the selective loss of G proteins in cilia of olfactory sensory neurons","volume":"104","author":"McEwen","year":"2007","journal-title":"PNAS"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"357","DOI":"10.2147\/CIA.S93820","article-title":"Effects of intravitreal ranibizumab on the untreated eye and systemic gene expression profile in age-related macular degeneration","volume":"11","author":"Michalska-Ma\u0142ecka","year":"2016","journal-title":"Clinical Interventions in Aging"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.stem.2019.03.009","article-title":"Drug screening in human PSC-cardiac organoids identifies pro-proliferative compounds acting via the mevalonate pathway","volume":"24","author":"Mills","year":"2019","journal-title":"Cell Stem Cell"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"2861","DOI":"10.1101\/gad.1599207","article-title":"Autophagy: process and function","volume":"21","author":"Mizushima","year":"2007","journal-title":"Genes & Development"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.celrep.2018.09.043","article-title":"A CEP290 C-terminal domain complements the mutant CEP290 of rd16 mice in trans and rescues retinal degeneration","volume":"25","author":"Mookherjee","year":"2018","journal-title":"Cell Reports"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1016\/j.stem.2012.05.009","article-title":"Self-formation of optic CUPS and storable stratified neural retina from human escs","volume":"10","author":"Nakano","year":"2012","journal-title":"Cell Stem Cell"},{"key":"bib72","first-page":"176","article-title":"Effects of various pharmacologic agents on allergic inflammation of the eye. The roles of chemical mediators in ocular inflammation","volume":"19","author":"Okada","year":"1980","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"bib73","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2121875119","article-title":"Compartmentalized citrullination in Muller glial endfeet during retinal degeneration","volume":"119","author":"Palko","year":"2022","journal-title":"PNAS"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/nature12639","article-title":"Functional interaction between autophagy and ciliogenesis","volume":"502","author":"Pampliega","year":"2013","journal-title":"Nature"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/j.stem.2016.03.021","article-title":"Identification and correction of mechanisms underlying inherited blindness in human ipsc-derived optic CUPS","volume":"18","author":"Parfitt","year":"2016","journal-title":"Cell Stem Cell"},{"key":"bib76","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a017285","article-title":"The status of RPE65 gene therapy trials: safety and efficacy","volume":"5","author":"Pierce","year":"2015","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/s41556-022-00869-0","article-title":"Aggresome assembly at the centrosome is driven by CP110-CEP97-CEP290 and centriolar satellites","volume":"24","author":"Prosser","year":"2022","journal-title":"Nature Cell Biology"},{"key":"bib78","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1016\/j.cell.2007.04.035","article-title":"HEF1-dependent Aurora A activation induces disassembly of the primary cilium","volume":"129","author":"Pugacheva","year":"2007","journal-title":"Cell"},{"key":"bib79","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1780-1","article-title":"Shifting the balance of autophagy and proteasome activation reduces proteotoxic cell death: a novel therapeutic approach for restoring photoreceptor homeostasis","volume":"10","author":"Qiu","year":"2019","journal-title":"Cell Death & Disease"},{"key":"bib80","doi-asserted-by":"publisher","DOI":"10.1186\/2046-2530-1-22","article-title":"Photoreceptor sensory cilia and ciliopathies: focus on CEP290, RPGR and their interacting proteins","volume":"1","author":"Rachel","year":"2012","journal-title":"Cilia"},{"key":"bib81","doi-asserted-by":"publisher","first-page":"3775","DOI":"10.1093\/hmg\/ddv123","article-title":"Cep290 alleles in mice disrupt tissue-specific cilia biogenesis and recapitulate features of syndromic ciliopathies","volume":"24","author":"Rachel","year":"2015","journal-title":"Human Molecular Genetics"},{"key":"bib82","doi-asserted-by":"publisher","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"G: profiler: a web server for functional enrichment analysis and conversions of gene Lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Research"},{"key":"bib83","first-page":"97","article-title":"A simple and efficient method for generating human retinal organoids","volume":"26","author":"Regent","year":"2020","journal-title":"Molecular Vision"},{"key":"bib84","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.878351","article-title":"Nicotinamide promotes formation of retinal organoids from human pluripotent stem cells via enhanced neural cell fate commitment","volume":"16","author":"Regent","year":"2022","journal-title":"Frontiers in Cellular Neuroscience"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/nrm.2017.60","article-title":"Genes and molecular pathways underpinning ciliopathies","volume":"18","author":"Reiter","year":"2017","journal-title":"Nature Reviews. Molecular Cell Biology"},{"key":"bib86","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1007\/s10792-014-9921-0","article-title":"Significant reduction of diabetic macular edema following intravitreal ranibizumab injection in the fellow eye","volume":"34","author":"Rotsos","year":"2014","journal-title":"International Ophthalmology"},{"key":"bib87","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1159\/000228590","article-title":"The effect of intravitreal ranibizumab on the fellow untreated eye with subfoveal scarring due to exudative age-related macular degeneration","volume":"223","author":"Rouvas","year":"2009","journal-title":"Ophthalmologica. Journal International d\u2019ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde"},{"key":"bib88","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.stem.2022.01.002","article-title":"Cone photoreceptors in human stem cell-derived retinal organoids demonstrate intrinsic light responses that mimic those of primate fovea","volume":"29","author":"Saha","year":"2022","journal-title":"Cell Stem Cell"},{"key":"bib89","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.stem.2013.04.009","article-title":"Next-Generation regenerative medicine: organogenesis from stem cells in 3D culture","volume":"12","author":"Sasai","year":"2013","journal-title":"Cell Stem Cell"},{"key":"bib90","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/ng1786","article-title":"The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4","volume":"38","author":"Sayer","year":"2006","journal-title":"Nature Genetics"},{"key":"bib91","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf2838","article-title":"Emerging therapies for inherited retinal degeneration","volume":"8","author":"Scholl","year":"2016","journal-title":"Science Translational Medicine"},{"key":"bib92","doi-asserted-by":"publisher","DOI":"10.3390\/biom11101528","article-title":"Pharmacological inhibition of the VCP\/proteasome axis rescues photoreceptor degeneration in rhop23h rat retinal explants","volume":"11","author":"Sen","year":"2021","journal-title":"Biomolecules"},{"key":"bib93","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.celrep.2017.06.045","article-title":"In vitro modeling using ciliopathy-patient-derived cells reveals distinct cilia dysfunctions caused by CEP290 mutations","volume":"20","author":"Shimada","year":"2017","journal-title":"Cell Reports"},{"key":"bib94","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-8-7","article-title":"Hdac6 as a target for neurodegenerative diseases: what makes it different from the other HDACs?","volume":"8","author":"Sim\u00f5es-Pires","year":"2013","journal-title":"Molecular Neurodegeneration"},{"key":"bib95","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1016\/j.celrep.2020.01.007","article-title":"Single-Cell transcriptomic comparison of human fetal retina, hpsc-derived retinal organoids, and long-term retinal cultures","volume":"30","author":"Sridhar","year":"2020","journal-title":"Cell Reports"},{"key":"bib96","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1124\/molpharm.120.000142","article-title":"The emerging role of neuronal organoid models in drug discovery: potential applications and hurdles to implementation","volume":"99","author":"Struzyna","year":"2021","journal-title":"Molecular Pharmacology"},{"key":"bib97","doi-asserted-by":"publisher","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The string database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Research"},{"key":"bib98","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/s41573-019-0049-9","article-title":"Therapies for rare diseases: therapeutic modalities, progress and challenges ahead","volume":"19","author":"Tambuyzer","year":"2020","journal-title":"Nature Reviews. Drug Discovery"},{"key":"bib99","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/nature12606","article-title":"Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites","volume":"502","author":"Tang","year":"2013","journal-title":"Nature"},{"key":"bib100","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041310","article-title":"Pathomechanisms of inherited retinal degeneration and perspectives for neuroprotection","volume":"1","author":"Tolone","year":"2022","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"key":"bib101","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1038\/s12276-021-00693-w","article-title":"M\u00fcller glial responses compensate for degenerating photoreceptors in retinitis pigmentosa","volume":"53","author":"Tomita","year":"2021","journal-title":"Experimental & Molecular Medicine"},{"key":"bib102","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108360","article-title":"The deubiquitinating enzyme ataxin-3 regulates ciliogenesis and phagocytosis in the retina","volume":"33","author":"Toulis","year":"2020","journal-title":"Cell Reports"},{"key":"bib103","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.devcel.2008.07.004","article-title":"Cp110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease","volume":"15","author":"Tsang","year":"2008","journal-title":"Developmental Cell"},{"key":"bib104","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/ng1805","article-title":"Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome","volume":"38","author":"Valente","year":"2006","journal-title":"Nature Genetics"},{"key":"bib105","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1242\/dmm.017913","article-title":"Biology and therapy of inherited retinal degenerative disease: insights from mouse models","volume":"8","author":"Veleri","year":"2015","journal-title":"Disease Models & Mechanisms"},{"key":"bib106","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1172\/JCI79766","article-title":"Activated mtorc1 promotes long-term cone survival in retinitis pigmentosa mice","volume":"125","author":"Venkatesh","year":"2015","journal-title":"The Journal of Clinical Investigation"},{"key":"bib107","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.182","article-title":"Tsc but not PTEN loss in starving cones of retinitis pigmentosa mice leads to an autophagy defect and mTORC1 dissociation from the lysosome","volume":"7","author":"Venkatesh","year":"2016","journal-title":"Cell Death & Disease"},{"key":"bib108","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.preteyeres.2018.03.005","article-title":"Non-Syndromic retinitis pigmentosa","volume":"66","author":"Verbakel","year":"2018","journal-title":"Progress in Retinal and Eye Research"},{"key":"bib109","doi-asserted-by":"publisher","first-page":"3698","DOI":"10.1242\/dev.146290","article-title":"Three-Dimensional automated reporter quantification (3D-ARQ) technology enables quantitative screening in retinal organoids","volume":"144","author":"Vergara","year":"2017","journal-title":"Development"},{"key":"bib110","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1080\/15548627.2022.2034131","article-title":"Treatments targeting autophagy ameliorate the age-related macular degeneration phenotype in mice lacking ApoE (apolipoprotein E)","volume":"18","author":"Vessey","year":"2022","journal-title":"Autophagy"},{"key":"bib111","doi-asserted-by":"publisher","first-page":"57","DOI":"10.2174\/1875397301004010057","article-title":"A grid algorithm for high throughput fitting of dose-response curve data","volume":"4","author":"Wang","year":"2010","journal-title":"Current Chemical Genomics"},{"key":"bib112","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2022.101157","article-title":"Proteostasis in aging-associated ocular disease","volume":"88","author":"Weinberg","year":"2022","journal-title":"Molecular Aspects of Medicine"},{"key":"bib113","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1016\/j.neuron.2017.06.008","article-title":"Enhanced functional genomic screening identifies novel mediators of dual leucine zipper kinase-dependent injury signaling in neurons","volume":"94","author":"Welsbie","year":"2017","journal-title":"Neuron"},{"key":"bib114","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/nrg2717","article-title":"Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait","volume":"11","author":"Wright","year":"2010","journal-title":"Nature Reviews. Genetics"},{"key":"bib115","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001034","article-title":"Cep290 is essential for the initiation of ciliary transition zone assembly","volume":"18","author":"Wu","year":"2020","journal-title":"PLOS Biology"},{"key":"bib116","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1016\/j.devcel.2022.06.015","article-title":"Distinct p53 isoforms code for opposing transcriptional outcomes","volume":"57","author":"Wylie","year":"2022","journal-title":"Developmental Cell"},{"key":"bib117","doi-asserted-by":"publisher","first-page":"207","DOI":"10.31662\/jmaj.2021-0090","article-title":"Autophagy and ciliogenesis","volume":"4","author":"Yamamoto","year":"2021","journal-title":"JMA Journal"},{"key":"bib118","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1080\/15548627.2018.1463121","article-title":"Inhibiting autophagy reduces retinal degeneration caused by protein misfolding","volume":"14","author":"Yao","year":"2018","journal-title":"Autophagy"},{"key":"bib119","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-017-0306-y","article-title":"The role of 5-HT receptors in depression","volume":"10","author":"Yohn","year":"2017","journal-title":"Molecular Brain"},{"key":"bib120","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17821-1","article-title":"Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy","volume":"11","author":"Zaninello","year":"2020","journal-title":"Nature Communications"},{"key":"bib121","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.tig.2018.01.002","article-title":"Rna biology in retinal development and disease","volume":"34","author":"Zelinger","year":"2018","journal-title":"Trends in Genetics"},{"key":"bib122","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57245","article-title":"Large-Scale phenotypic drug screen identifies neuroprotectants in zebrafish and mouse models of retinitis pigmentosa","volume":"10","author":"Zhang","year":"2021","journal-title":"eLife"},{"key":"bib123","doi-asserted-by":"publisher","first-page":"10866","DOI":"10.18632\/aging.202974","article-title":"Pharmacologic activation of autophagy without direct mTOR inhibition as a therapeutic strategy for treating dry macular degeneration","volume":"13","author":"Zhang","year":"2021","journal-title":"Aging"},{"key":"bib124","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5047","article-title":"Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs","volume":"5","author":"Zhong","year":"2014","journal-title":"Nature Communications"},{"key":"bib125","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2147\/OPTH.S69466","article-title":"Progression to macula-off tractional retinal detachment after a contralateral intraoperative intravitreal bevacizumab injection for proliferative diabetic retinopathy","volume":"9","author":"Zlotcavitch","year":"2015","journal-title":"Clinical Ophthalmology"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/83205\/elife-83205-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/83205\/elife-83205-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/83205","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:09:45Z","timestamp":1697058585000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/83205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,28]]},"references-count":125,"alternative-id":["10.7554\/eLife.83205"],"URL":"https:\/\/doi.org\/10.7554\/elife.83205","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.09.14.22279917","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2022.09.14.22279917","asserted-by":"object"}],"is-supplemented-by":[{"id-type":"accession","id":"GSE206959","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.83205.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.83205.sa0","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.83205.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,28]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e83205"}}