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ADOA is characterized by the degeneration of retinal ganglion cells (RGCs). This causes visual loss, which can lead to legal blindness in many cases. Nowadays, there is no effective treatment for ADOA. In this article, we have established an isogenic human RGC model for ADOA using iPSC technology and the genome editing tool CRISPR\/Cas9 from a previously generated iPSC line of an ADOA plus patient harboring the pathogenic variant NM_015560.3: c.1861C&gt;T (p.Gln621Ter) in heterozygosis in OPA1. To this end, a protocol based on supplementing the iPSC culture media with several small molecules and defined factors trying to mimic embryonic development has been employed. Subsequently, the created model was validated, confirming the presence of a defect of intergenomic communication, impaired mitochondrial respiration, and an increase in apoptosis and ROS generation. Finally, we propose the analysis of OPA1 expression by qPCR as an easy read-out method to carry out future drug screening studies using the created RGC model. In summary, this model provides a useful platform for further investigation of the underlying pathophysiological mechanisms of ADOA plus and for testing compounds with potential pharmacological action.<\/jats:p>","DOI":"10.3390\/ijms25137240","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:58:42Z","timestamp":1719925122000},"page":"7240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Creation of an Isogenic Human iPSC-Based RGC Model of Dominant Optic Atrophy Harboring the Pathogenic Variant c.1861C&gt;T (p.Gln621Ter) in the OPA1 Gene"],"prefix":"10.3390","volume":"25","author":[{"given":"Marta","family":"Garc\u00eda-L\u00f3pez","sequence":"first","affiliation":[{"name":"Grupo de Investigaci\u00f3n Traslacional con C\u00e9lulas iPS, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, 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\u00c1ngel","family":"Mart\u00edn","sequence":"additional","affiliation":[{"name":"Servicio de Gen\u00e9tica, Hospital 12 de Octubre, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Laboratorio de Enfermedades Mitocondriales y Neuromusculares, Instituto de Investigaci\u00f3n Sanitaria Hospital 12 de Octubre (imas12), 28041 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9242-7065","authenticated-orcid":false,"given":"Carmen","family":"Ayuso","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain"},{"name":"Department of Genetics & Genomics, Instituto de Investigaci\u00f3n Sanitaria-Fundaci\u00f3n Jim\u00e9nez D\u00edaz University Hospital, Universidad 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Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.preteyeres.2010.11.002","article-title":"Mitochondrial optic neuropathies\u2014Disease mechanisms and therapeutic strategies","volume":"30","author":"Griffiths","year":"2011","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1750-1172-7-46","article-title":"Dominant optic atrophy","volume":"7","author":"Lenaers","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.spen.2017.06.001","article-title":"Dominant Optic Atrophy and Leber\u2019s Hereditary Optic Neuropathy: Update on clinical features and current therapeutic approaches","volume":"24","author":"Chun","year":"2017","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/brain\/awq007","article-title":"Multi-system neurological disease is common in patients with OPA1 mutations","volume":"133","author":"Griffiths","year":"2010","journal-title":"Brain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/acn3.51026","article-title":"Idebenone increases chance of stabilization\/recovery of visual acuity in OPA1-dominant optic atrophy","volume":"7","author":"Romagnoli","year":"2020","journal-title":"Ann. Clin. Traslational Neurol."},{"key":"ref_11","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":"ref_12","doi-asserted-by":"crossref","first-page":"275","DOI":"10.4252\/wjsc.v11.i7.375","article-title":"Predicting differentiation potential of human pluripotent stem cells: Possibilities and challenges","volume":"11","author":"Liu","year":"2019","journal-title":"World J. Stem Cells"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.bbrc.2009.02.120","article-title":"Differentiation and characterization of embryonic stem cells into three germ layers","volume":"381","author":"Shiraki","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1089\/biores.2019.0046","article-title":"Induced pluripotent stem cells: Reprogramming platforms and applications in cell replacement therapy","volume":"9","author":"Ngai","year":"2020","journal-title":"BioRes. Open Access"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Aboul-Soud, M.A.M., Alzahrani, A.J., and Mahmoud, A. (2021). Induced pluripotent stem cells (iPSCs)\u2014Roles in regenerative therapies, disease modelling and drug screening. Cells, 10.","DOI":"10.3390\/cells10092319"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5970","DOI":"10.1167\/iovs.09-4504","article-title":"Generation of retinal ganglion-like cells from reprogrammed mouse fibroblasts","volume":"51","author":"Chen","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1167\/tvst.3.3.7","article-title":"Methods of retinal ganglion cell differentiation from puripotent stem cells","volume":"3","author":"Gill","year":"2014","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity","volume":"337","author":"Jinek","year":"2012","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/bfgp\/elw025","article-title":"CRISPR-Cas9 technology: Applications and human disease modelling","volume":"16","year":"2017","journal-title":"Brief. Funct. Genom."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.scr.2016.03.011","article-title":"Generation of a human iPSC line from a patient with an optic atrophy \u2018plus\u2019 phenotype due to a mutation in the OPA1 gene","volume":"16","author":"Fraga","year":"2016","journal-title":"Stem Cell Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/978-1-4939-9170-9_11","article-title":"Editing the genome of human induced pluripotent stem cells using CRISPR\/Cas9 ribonucleoprotein complexes","volume":"1961","author":"Bruntraeger","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102108","DOI":"10.1016\/j.scr.2020.102108","article-title":"Generation of the iPSC line IISHDOi007\u2014A from peripheral blood mononuclear cells from a patient with McArdle disease harbouring the mutation c.2392 T > C; p.Trp798Arg","volume":"49","author":"Cerrada","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_23","first-page":"3531","article-title":"Defined conditions for differentiation of functional retinal ganglion cells from human pluripotent stem cells","volume":"59","author":"Lee","year":"2018","journal-title":"Retin. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1007\/s12015-010-9138-1","article-title":"Robust enhancement of neural differentiation from human ES and iPS cells regardless of their innate difference in differentiation propensity","volume":"6","author":"Kim","year":"2010","journal-title":"Stem Cell Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.stem.2013.04.008","article-title":"Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells","volume":"12","author":"Maroof","year":"2013","journal-title":"Cell Stem Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S1534-5807(01)00069-7","article-title":"Neural and head induction by insulin-like growth factor signals","volume":"1","author":"Pera","year":"2001","journal-title":"Dev. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1159\/000090759","article-title":"Notch activity is downregulated just prior to retinal ganglion cell differentiation","volume":"28","author":"Nelson","year":"2006","journal-title":"Dev. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1523\/JNEUROSCI.19-09-03277.1999","article-title":"Brain-derived neurotrophic factor mediates the anti-apoptotic effect of NMDA in cerebellar granule neurons: Signal transduction cascades and site of ethanol action","volume":"19","author":"Bhave","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"100824","DOI":"10.1016\/j.preteyeres.2019.100824","article-title":"Recapitulating developmental mechanisms for retinal regeneration","volume":"76","author":"Ahmad","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_31","first-page":"258","article-title":"Roles and regulation of Thy-1, a context-dependent modulator of cell phenotype","volume":"35","author":"Bradley","year":"2009","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1093\/hmg\/ddac128","article-title":"Modelling autosomal dominant optic atrophy associated with OPA1 variants in iPSC-derived retinal ganglion cells","volume":"31","author":"Sladen","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13287-015-0264-1","article-title":"Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets","volume":"7","author":"Chen","year":"2016","journal-title":"Stem Cell Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/j.1750-3639.2000.tb00277.x","article-title":"Defects of intergenomic communication: Where do we stand?","volume":"10","author":"Hirano","year":"2000","journal-title":"Brain Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1093\/brain\/awm272","article-title":"Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: A novel disorder of mtDNA maintenance","volume":"131","author":"Hudson","year":"2008","journal-title":"Brain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1212\/01.WNL.0000157282.76715.B1","article-title":"Mitochondrial DNA content is decreased in autosomal dominant optic atrophy","volume":"64","author":"Kim","year":"2005","journal-title":"Neurology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1001\/archneurol.2010.228","article-title":"Defective mitochondrial adenosine triphosphate production in skeletal muscle from patients with dominant optic atrophy due to OPA1 mutations","volume":"68","author":"Lodi","year":"2011","journal-title":"Arch. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Varum, S., Rodrigues, A.S., Moura, M.B., Momcilovic, O., Easley IV, C.A., Ramalho-Santos, J., van Houten, B., and Schatten, G. (2011). Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020914"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4067162","DOI":"10.1155\/2019\/4067162","article-title":"Mitochondrial role in stemness and differentiation of hematopoietic stem cells","volume":"2019","author":"Papa","year":"2019","journal-title":"Stem Cells Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1167\/iovs.14-16288","article-title":"Lo Changes in mitochondrial morphology and bioenergetics in human lymphoblastoid cells with four novel opa1 mutations","volume":"56","author":"Kao","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S151","DOI":"10.1016\/S0039-6257(99)00029-6","article-title":"Apoptosis of Retinal Ganglion Cells in Glaucoma","volume":"43","author":"Nickells","year":"1999","journal-title":"Surv. Ophthalmol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1089\/neu.1999.16.153","article-title":"Apoptotic versus necrotic characteristics of retinal ganglion cell death after partial optic nerve injury","volume":"16","author":"Bien","year":"1999","journal-title":"J. Neurotrauma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1136\/bjo.83.8.980","article-title":"Ganglion cell death in glaucoma: What do we really know?","volume":"83","author":"Osborne","year":"1999","journal-title":"Br. J. Ophthalmol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/ana.21385","article-title":"Hereditary optic neuropathies share a common mitochondrial coupling defect","volume":"63","author":"Chevrollier","year":"2008","journal-title":"Ann. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1093\/brain\/awm335","article-title":"OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion","volume":"131","author":"Zanna","year":"2008","journal-title":"Brain"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1055\/s-0035-1563574","article-title":"Therapeutic approaches to inherited optic neuropathies","volume":"35","year":"2015","journal-title":"Semin. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"E692","DOI":"10.1002\/humu.21025","article-title":"Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations","volume":"30","author":"Bonneau","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/humu.20607","article-title":"Comprehensive cDNA study and quantitative transcript analysis of mutant OPA1 transcript containing premature termination codons","volume":"29","author":"Schimpf","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7729","DOI":"10.1038\/srep07729","article-title":"Method for quantitative analysis of nonsense-mediated mRNA decay at the single cell level","volume":"5","author":"Pereverzev","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1179\/135100099101534882","article-title":"Nicotinamide (vitamin B3) as an effective antioxidant against oxidative damage in rat brain mitochondria","volume":"4","author":"Kamat","year":"1998","journal-title":"Redox Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1111\/ceo.13818","article-title":"Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial","volume":"48","author":"Hui","year":"2020","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.omtn.2017.08.003","article-title":"USH2A gene editing using the CRISPR system","volume":"8","author":"Jaijo","year":"2017","journal-title":"Mol. Ther. Nucleic Acid"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"19511","DOI":"10.1002\/jcp.28549","article-title":"The mutation m.13513G>A impairs cardiac function, favoring a neuroectoderm commitment, in a mutant-load dependent way","volume":"234","author":"Garesse","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.scr.2017.07.020","article-title":"Establishment of a human iPSC line (IISHDOi001-A) from a patient with McArdle disease","volume":"23","author":"Garesse","year":"2017","journal-title":"Stem Cell Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1093\/brain\/awm298","article-title":"OPA1 mutations induce mitochondrial DNA instability and optic atrophy \u201cplus\u201d phenotypes","volume":"131","author":"Valentino","year":"2008","journal-title":"Brain"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101566","DOI":"10.1016\/j.scr.2019.101566","article-title":"Derivation of a human DOA iPSC line, IISHDOi006-A, with a mutation in the ACO2 gene: c.1999G>A; p.Glu667Lys","volume":"40","author":"Cerrada","year":"2019","journal-title":"Stem Cell Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7240\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:08:16Z","timestamp":1760108896000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/7240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,30]]},"references-count":56,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25137240"],"URL":"https:\/\/doi.org\/10.3390\/ijms25137240","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,30]]}}}