{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:55:35Z","timestamp":1787500535068,"version":"build-2736575974"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2700902"],"award-info":[{"award-number":["2021YFC2700902"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970557"],"award-info":[{"award-number":["31970557"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81900904"],"award-info":[{"award-number":["81900904"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Leber\u2019s hereditary optic neuropathy (LHON) is a maternally inherited eye disease that results from degeneration of retinal ganglion cells (RGC). Mitochondrial ND4 11778G\u2009&amp;gt;\u2009A mutation, which affects structural components of complex I, is the most prevalent LHON-associated mitochondrial DNA (mtDNA) mutation worldwide. The m.11778G\u2009&amp;gt;\u2009A mutation is the primary contributor underlying the development of LHON and X-linked PRICKLE3 allele (c.157C\u2009&amp;gt;\u2009T, p.Arg53Trp) linked to biogenesis of ATPase interacts with m.11778G\u2009&amp;gt;\u2009A mutation to cause LHON. However, the lack of appropriate cell and animal models of LHON has been significant obstacles for deep elucidation of disease pathophysiology, specifically the tissue-specific effects. Using RGC-like cells differentiated from induced pluripotent stem cells (iPSCs) from members of one Chinese family (asymptomatic subjects carrying only m.11778G\u2009&amp;gt;\u2009A mutation or PRICKLE3 p.Arg53Trp mutation, symptomatic individuals bearing both m.11778G\u2009&amp;gt;\u2009A and PRICKLE3 p.Arg53Trp mutations and control lacking these mutations), we demonstrated the deleterious effects of mitochondrial dysfunctions on the morphology and functions of RGCs. Notably, iPSCs bearing only m.11778G\u2009&amp;gt;\u2009A or p.Arg53Trp mutation exhibited mild defects in differentiation to RGC-like cells. The RGC-like cells carrying only m.11778G\u2009&amp;gt;\u2009A or p.Arg53Trp mutation displayed mild defects in RGC morphology, including the area of soma and numbers of neurites, electrophysiological properties, ATP contents and apoptosis. Strikingly, those RGC-like cells derived from symptomatic individuals harboring both m.11778G\u2009&amp;gt;\u2009A and p.Arg53Trp mutations displayed greater defects in the development, morphology and functions than those in cells bearing single mutation. These findings provide new insights into pathophysiology of LHON arising from RGC deficiencies caused by synergy between m.11778G\u2009&amp;gt;\u2009A and PRICKLE3 p.Arg53Trp mutation.<\/jats:p>","DOI":"10.1093\/hmg\/ddac190","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T18:24:36Z","timestamp":1660155876000},"page":"231-243","source":"Crossref","is-referenced-by-count":22,"title":["Abnormal morphology and function in retinal ganglion cells derived from patients-specific iPSCs generated from individuals with Leber\u2019s hereditary optic neuropathy"],"prefix":"10.1093","volume":"32","author":[{"given":"Zhipeng","family":"Nie","sequence":"first","affiliation":[{"name":"Division of Medical Genetics and Genomics , The Children\u2019s Hospital, , Hangzhou, Zhejiang , China"},{"name":"Zhejiang University School of Medicine and National Clinical Research Center for Child Health , The Children\u2019s Hospital, , Hangzhou, Zhejiang , China"},{"name":"Institute of Genetics and Department of Human Genetics, Zhejiang University School of Medicine , Hangzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Department of Human Genetics, Zhejiang University School of Medicine , Hangzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarong","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics , The Children\u2019s Hospital, , Hangzhou, Zhejiang , China"},{"name":"Zhejiang University School of Medicine and National Clinical Research Center for Child Health , The Children\u2019s Hospital, , Hangzhou, Zhejiang , China"},{"name":"Institute of Genetics and Department of Human Genetics, Zhejiang University School of Medicine , Hangzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchun","family":"Ji","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics , The Children\u2019s Hospital, , Hangzhou, Zhejiang , China"},{"name":"Zhejiang University School of Medicine and National Clinical Research Center for Child Health , The Children\u2019s Hospital, , Hangzhou, Zhejiang , China"},{"name":"Institute of Genetics and Department of Human Genetics, Zhejiang University School of Medicine , Hangzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital, Shandong First Medical University , Jinan, Shandong , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University , Wenzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1115-561X","authenticated-orcid":false,"given":"Xiangtian","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University , Wenzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5067-6736","authenticated-orcid":false,"given":"Min-Xin","family":"Guan","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomics , The Children\u2019s Hospital, , Hangzhou, Zhejiang , China"},{"name":"Zhejiang University School of Medicine and National Clinical Research Center for Child Health , The Children\u2019s Hospital, , Hangzhou, Zhejiang , China"},{"name":"Institute of Genetics and Department of Human Genetics, Zhejiang University School of Medicine , Hangzhou, Zhejiang , China"},{"name":"Department of Ophthalmology, The First Affiliated Hospital, Shandong First Medical University , Jinan, Shandong , China"},{"name":"Zhejiang Provincial Key Lab of Genetic and Developmental Disorder , Hangzhou, Zhejiang , China"},{"name":"Joint Institute of Genetics and Genomic Medicine Between Zhejiang University and University of Toronto, Zhejiang University , Hangzhou, Zhejiang , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"2023011411265023700_ref1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/164_2017_2","article-title":"Leber hereditary optic neuropathy: Exemplar of an mtDNA disease","volume":"240","author":"Wallace","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"2023011411265023700_ref2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11940-010-0100-y","article-title":"Leber\u2019s hereditary optic neuropathy","volume":"13","author":"Sadun","year":"2011","journal-title":"Curr. Treat. Options Neurol."},{"key":"2023011411265023700_ref3","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.bbabio.2009.02.024","article-title":"Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders","volume":"1787","author":"Carelli","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"2023011411265023700_ref4","doi-asserted-by":"crossref","first-page":"676187","DOI":"10.3389\/fmolb.2021.676187","article-title":"Selective neuron vulnerability in common and rare diseases-mitochondria in the focus","volume":"8","author":"Pa\u00df","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"2023011411265023700_ref5","first-page":"295","article-title":"Clinical spectrum of Leber's hereditary optic neuropathy","volume":"4","author":"Kerrison","year":"1997","journal-title":"Clin. Neurosci."},{"key":"2023011411265023700_ref6","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1126\/science.3201231","article-title":"Mitochondrial DNA mutation associated with Leber\u2019s hereditary optic neuropathy","volume":"242","author":"Wallace","year":"1988","journal-title":"Science"},{"key":"2023011411265023700_ref7","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/humu.1380060405","article-title":"Phylogenetic analysis of Leber\u2019s hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations","volume":"6","author":"Brown","year":"1995","journal-title":"Hum. Mutat."},{"key":"2023011411265023700_ref8","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1136\/jmg.2007.054270","article-title":"Inherited mitochondrial optic neuropathies","volume":"46","author":"Yu-Wai-Man","year":"2009","journal-title":"J. Med. Genet."},{"key":"2023011411265023700_ref9","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/02713689808951221","article-title":"Spectrum of pathogenic mitochondrial DNA mutations and clinical features in Japanese families with Leber's hereditary optic neuropathy","volume":"17","author":"Mashima","year":"1998","journal-title":"Curr. Eye Res."},{"key":"2023011411265023700_ref10","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1167\/iovs.14-16158","article-title":"Prevalence of mitochondrial ND4 mutations in 1281 Han Chinese subjects with Leber\u2019s hereditary optic neuropathy","volume":"56","author":"Jiang","year":"2015","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023011411265023700_ref11","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1167\/iovs.13-13011","article-title":"Frequency and spectrum of mitochondrial ND6 mutations in 1218 Han Chinese subjects with Leber\u2019s hereditary optic neuropathy","volume":"55","author":"Liang","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023011411265023700_ref12","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1167\/iovs.16-19243","article-title":"Mitochondrial ND1 variants in 1281 Chinese subjects with Leber\u2019s hereditary optic neuropathy","volume":"57","author":"Ji","year":"2016","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023011411265023700_ref13","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/S0002-9394(14)76784-4","article-title":"The clinical characteristics of pedigrees of Leber\u2019s hereditary optic neuropathy with the 11778 mutation","volume":"111","author":"Newman","year":"1991","journal-title":"Am J. Ophthalmol."},{"key":"2023011411265023700_ref14","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1093\/brain\/118.2.319","article-title":"The clinical features of Leber's hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation","volume":"118","author":"Riordan-Eva","year":"1995","journal-title":"Brain"},{"key":"2023011411265023700_ref15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.ymgme.2010.04.013","article-title":"Very high penetrance and occurrence of Leber's hereditary optic neuropathy in a large Han Chinese pedigree carrying the ND4 G11778A mutation","volume":"100","author":"Zhou","year":"2010","journal-title":"Mol. Genet. Metab."},{"key":"2023011411265023700_ref16","doi-asserted-by":"crossref","first-page":"13155","DOI":"10.1074\/jbc.271.22.13155","article-title":"Respiration and growth defects in transmitochondrial cell lines carrying the 11778 mutation associated with Leber\u2019s hereditary optic neuropathy","volume":"271","author":"Hofhaus","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2023011411265023700_ref17","doi-asserted-by":"crossref","first-page":"39831","DOI":"10.1074\/jbc.M006476200","article-title":"Functional analysis of lymphoblast and cybrid mitochondria containing the 3460, 11778, or 14484 Leber\u2019s hereditary optic neuropathy mitochondrial DNA mutation","volume":"275","author":"Brown","year":"2000","journal-title":"J. Biol. Chem."},{"key":"2023011411265023700_ref18","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1093\/hmg\/ddv498","article-title":"The exome sequencing identified the mutation in YARS2 encoding the mitochondrial tyrosyl-tRNA synthetase as a nuclear modifier for the phenotypic manifestation of Leber\u2019s hereditary optic neuropathy-associated mitochondrial DNA mutation","volume":"25","author":"Jiang","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"2023011411265023700_ref19","doi-asserted-by":"crossref","first-page":"4001","DOI":"10.1093\/hmg\/ddn303","article-title":"Mitochondrial DNA background modulates the assembly kinetics of OXPHOS complexes in a cellular model of mitochondrial disease","volume":"17","author":"Pello","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"2023011411265023700_ref20","doi-asserted-by":"crossref","first-page":"13224","DOI":"10.1074\/jbc.RA120.014603","article-title":"Complex I mutations synergize to worsen the phenotypic expression of Leber\u2019s hereditary optic neuropathy","volume":"295","author":"Ji","year":"2020","journal-title":"J. Biol. Chem."},{"key":"2023011411265023700_ref21","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1093\/hmg\/ddy450","article-title":"Contribution of mitochondrial ND1 3394T&gt;C mutation to the phenotypic manifestation of Leber\u2019s hereditary optic neuropathy","volume":"28","author":"Ji","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"2023011411265023700_ref22","doi-asserted-by":"crossref","first-page":"8198","DOI":"10.1073\/pnas.88.18.8198","article-title":"X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: evidence from segregation analysis for dependence on X chromosome inactivation","volume":"88","author":"Bu","year":"1991","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2023011411265023700_ref23","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1086\/498176","article-title":"Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder","volume":"77","author":"Hudson","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"2023011411265023700_ref24","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1167\/iovs.62.7.22","article-title":"Leber\u2019s Hereditary Optic Neuropathy arising from the synergy between YARS2 mutation and mitochondrial ND1 3635G&gt;A mutations","volume":"62","author":"Jin","year":"2021","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023011411265023700_ref25","doi-asserted-by":"crossref","first-page":"4935","DOI":"10.1172\/JCI134965","article-title":"PRICKLE3 linked to ATPase biogenesis manifested Leber's hereditary optic neuropathy","volume":"130","author":"Yu","year":"2020","journal-title":"J. Clin. Invest."},{"key":"2023011411265023700_ref26","doi-asserted-by":"crossref","first-page":"165743","DOI":"10.1016\/j.bbadis.2020.165743","article-title":"Emerging model systems and treatment approaches for Leber's hereditary optic neuropathy: challenges and opportunities","volume":"1866","author":"Bahr","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. basis Dis."},{"key":"2023011411265023700_ref27","doi-asserted-by":"crossref","first-page":"20065","DOI":"10.1073\/pnas.1217113109","article-title":"Mouse mtDNA mutant model of Leber hereditary optic neuropathy","volume":"109","author":"Lin","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2023011411265023700_ref28","doi-asserted-by":"crossref","first-page":"648916","DOI":"10.3389\/fneur.2021.648916","article-title":"Exploiting hiPSCs in Leber's hereditary optic neuropathy (LHON): present achievements and future perspectives","volume":"12","author":"Peron","year":"2021","journal-title":"Front. Neurol."},{"key":"2023011411265023700_ref29","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1093\/hmg\/ddaa063","article-title":"Mitochondrial transport mediates survival of retinal ganglion cells in affected LHON patients","volume":"29","author":"Yang","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"2023011411265023700_ref30","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/7651_2015_204","article-title":"Generation of integration-free patient specific iPS cells using episomal plasmids under feeder free conditions","volume":"1353","author":"Caxaria","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"2023011411265023700_ref31","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of pluripotent stem cells from adult human fibroblasts by defined factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"2023011411265023700_ref32","doi-asserted-by":"crossref","first-page":"424","DOI":"10.5966\/sctm.2013-0147","article-title":"Chemically induced specification of retinal ganglion cells from human embryonic and induced pluripotent stem cells","volume":"3","author":"Riazifar","year":"2014","journal-title":"Stem Cells Transl. Med."},{"key":"2023011411265023700_ref33","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.yexcr.2018.01.020","article-title":"Bioactivity and gene expression profiles of hiPSC-generated retinal ganglion cells in MT-ND4 mutated Leber's hereditary optic neuropathy","volume":"363","author":"Wu","year":"2018","journal-title":"Exp. Cell Res."},{"key":"2023011411265023700_ref34","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1002\/sctm.17-0059","article-title":"Enhanced stem cell differentiation and immunopurification of genome engineered human retinal ganglion cells","volume":"6","author":"Sluch","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"2023011411265023700_ref35","first-page":"152","article-title":"Differentiation of retinal ganglion cells from induced pluripotent stem cells: a review","volume":"12","author":"Ji","year":"2019","journal-title":"Int. J. Ophthalmol."},{"key":"2023011411265023700_ref36","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.gene.2013.07.101","article-title":"Onset of rosette formation during spontaneous neural differentiation of hESC and hiPSC colonies","volume":"534","author":"Malchenko","year":"2014","journal-title":"Gene"},{"key":"2023011411265023700_ref37","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3390\/cells8060625","article-title":"Glutamate stimulation dysregulates AMPA receptors-induced signal transduction pathway in Leber's inherited optic neuropathy patient-specific hiPSC-derived retinal ganglion cells","volume":"8","author":"Yang","year":"2019","journal-title":"Cells"},{"key":"2023011411265023700_ref38","doi-asserted-by":"crossref","first-page":"30552","DOI":"10.1038\/srep30552","article-title":"Enriched retinal ganglion cells derived from human embryonic stem cells","volume":"6","author":"Gill","year":"2016","journal-title":"Sci. Rep."},{"key":"2023011411265023700_ref39","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/stem.2513","article-title":"Generation of functional human retinal ganglion cells with target specificity from pluripotent stem cells by chemically defined recapitulation of developmental mechanism","volume":"35","author":"Teotia","year":"2017","journal-title":"Stem Cells"},{"key":"2023011411265023700_ref40","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.stemcr.2018.12.010","article-title":"Astrocytes regulate the development and maturation of retinal ganglion cells derived from human pluripotent stem cells","volume":"12","author":"Vander Wall","year":"2019","journal-title":"Stem Cell Reports."},{"key":"2023011411265023700_ref41","doi-asserted-by":"crossref","first-page":"8039","DOI":"10.1093\/nar\/gku466","article-title":"A deafness-associated tRNAHis mutation alters the mitochondrial function, ROS production and membrane potential","volume":"42","author":"Gong","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2023011411265023700_ref42","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.mito.2011.06.006","article-title":"The altered activity of complex III may contribute to the high penetrance of Leber\u2019s hereditary optic neuropathy in a Chinese family carrying the ND4 G11778A mutation","volume":"11","author":"","year":"2011","journal-title":"Mitochondrion."},{"key":"2023011411265023700_ref43","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1093\/hmg\/ddy107","article-title":"Leber's hereditary optic neuropathy (LHON)-associated ND5 12338T &gt; C mutation altered the assembly and function of complex I, apoptosis and mitophagy","volume":"27","author":"Zhang","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"2023011411265023700_ref44","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1167\/iovs.62.9.38","article-title":"Association between Leber's hereditary optic neuropathy and MT-ND1 3460G&gt;A mutation-induced alterations in mitochondrial function, apoptosis, and mitophagy","volume":"62","author":"Zhang","year":"2021","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2023011411265023700_ref45","doi-asserted-by":"crossref","first-page":"C723","DOI":"10.1152\/ajpcell.00462.2010","article-title":"A practical guide to evaluating colocalization in biological microscopy","volume":"300","author":"Dunn","year":"2011","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"2023011411265023700_ref46","doi-asserted-by":"crossref","first-page":"100816","DOI":"10.1016\/j.jbc.2021.100816","article-title":"Mechanistic insights into mitochondrial tRNAAla 3\u2032-end metabolism deficiency","volume":"297","author":"Ji","year":"2021","journal-title":"J. Biol. Chem."},{"key":"2023011411265023700_ref47","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","article-title":"Emerging roles of caspase-3 in apoptosis","volume":"6","author":"Porter","year":"1999","journal-title":"Cell Death Differ."},{"key":"2023011411265023700_ref48","doi-asserted-by":"crossref","first-page":"9384","DOI":"10.1158\/0008-5472.CAN-08-2655","article-title":"SM-164: a novel, bivalent Smac mimetic that induces apoptosis and tumor regression by concurrent removal of the blockade of cIAP-1\/2 and XIAP","volume":"68","author":"Lu","year":"2008","journal-title":"Cancer Res."},{"key":"2023011411265023700_ref49","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1023\/A:1020546615229","article-title":"TNF-induced signaling in apoptosis","volume":"19","author":"Rath","year":"1999","journal-title":"J. Clin. Immunol."},{"key":"2023011411265023700_ref50","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/cne.903000103","article-title":"Topography of ganglion cells in human retina","volume":"300","author":"Curcio","year":"1990","journal-title":"J. Comp. Neurol."},{"key":"2023011411265023700_ref51","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/hmg\/ddx273","article-title":"Optic neuropathies: the tip of the neurodegeneration iceberg","volume":"26","author":"Carelli","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"2023011411265023700_ref52","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.1093\/brain\/awq218","article-title":"Opa1 deficiency in a mouse model of dominant optic atrophy leads to retinal ganglion cell dendropathy","volume":"133","author":"Williams","year":"2010","journal-title":"Brain"},{"key":"2023011411265023700_ref53","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.136046","article-title":"Mutations of MAP1B encoding a microtubule-associated phosphoprotein cause sensorineural hearing loss","volume":"5","author":"Cui","year":"2020","journal-title":"JCI Insight."},{"key":"2023011411265023700_ref54","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1093\/bioinformatics\/btr390","article-title":"Simple Neurite Tracer: open source software for reconstruction, visualization and analysis of neuronal processes","volume":"27","author":"Longair","year":"2011","journal-title":"Bioinformatics"},{"key":"2023011411265023700_ref55","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/cyto.a.20022","article-title":"Design and validation of a tool for neurite tracing and analysis in fluorescence microscopy images","volume":"58","author":"Meijering","year":"2004","journal-title":"Cytometry A"},{"key":"2023011411265023700_ref56","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/nmeth.3125","article-title":"Neuronal morphometry directly from bitmap images","volume":"11","author":"Ferreira","year":"2014","journal-title":"Nat. Methods"},{"key":"2023011411265023700_ref57","article-title":"Genetic correction of TRMU allele restored the mitochondrial dysfunction-induced deficiencies in iPSCs-derived hair cells of hearing-impaired patients","volume":"2022 Apr 25","author":"Chen","year":"2022","journal-title":"Hum. Mol. Genet."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddac190\/45922110\/ddac190.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/32\/2\/231\/48520212\/ddac190.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/32\/2\/231\/48520212\/ddac190.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,14]],"date-time":"2023-01-14T06:28:39Z","timestamp":1673677719000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/32\/2\/231\/6659966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,10]]},"references-count":57,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,8,10]]},"published-print":{"date-parts":[[2023,1,6]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddac190","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,15]]},"published":{"date-parts":[[2022,8,10]]}}}