{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T17:43:14Z","timestamp":1794246194188,"version":"4.9.0"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>Preferential degeneration of retinal ganglion cells (RGCs) is a defining feature of the inherited optic neuropathies (IONs), a group of monogenic eye diseases predominately comprising Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). Their pathogenesis is characterised by mitochondrial dysfunction, which causes loss of RGCs leading to irreversible vision loss. Although currently incurable, there are several emerging therapeutic avenues encompassing gene therapies, precision medicine strategies and neuroprotection. These are underscored by recent technological advances such as next-generation sequencing and improved disease modelling. In this review, we discuss these advances and the impact these will have on future diagnostic and treatment capabilities. We first focus on the clinical presentation and pathogenic mechanisms of LHON and DOA, followed by a discussion of emerging technology to facilitate diagnosis and treatment. We highlight the current unmet clinical demand of IONs, and the promise of current and future research developments.<\/jats:p>","DOI":"10.3389\/fneur.2025.1609033","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T05:25:37Z","timestamp":1753421137000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Technological advances in the diagnosis and management of inherited optic neuropathies"],"prefix":"10.3389","volume":"16","author":[{"given":"John O. T.","family":"Britton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Yu-Wai-Man","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benson S.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1016\/j.ophtha.2011.02.027","article-title":"Retinal nerve fiber layer thickness in dominant optic atrophy: measurements by optical coherence tomography and correlation with age","volume":"118","author":"Barboni","year":"2011","journal-title":"Ophthalmology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"13205","DOI":"10.3390\/ijms232113205","article-title":"Solutions to a radical problem: overview of current and future treatment strategies in Leber\u2019s hereditary opic neuropathy","volume":"23","author":"Spiegel","year":"2022","journal-title":"Int J Mol Sci"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.mito.2017.08.014","article-title":"Mitochondrial dynamics, transport, and quality control: a bottleneck for retinal ganglion cell viability in optic neuropathies","volume":"36","author":"Ito","year":"2017","journal-title":"Mitochondrion"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"661938","DOI":"10.3389\/fneur.2021.661938","article-title":"Retinal ganglion cells\u2014diversity of cell types and clinical relevance","volume":"12","author":"Kim","year":"2021","journal-title":"Front Neurol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/fneur.2015.00005","article-title":"Dissociation of pupillary post-illumination responses from visual function in confirmed OPA1 c.983A\u202f>\u202fG and c.2708_2711delTTAG autosomal dominant optic atrophy","volume":"6","author":"Nissen","year":"2015","journal-title":"Front Neurol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1016\/j.neuroscience.2014.11.002","article-title":"The injury resistant ability of melanopsin-expressing intrinsically photosensitive retinal ganglion cells","volume":"284","author":"Cui","year":"2015","journal-title":"Neuroscience"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.1016\/j.ajhg.2021.09.015","article-title":"Establishing risk of vision loss in Leber hereditary optic neuropathy","volume":"108","author":"Lopez Sanchez","year":"2021","journal-title":"Am J Hum Genet"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1097\/WNO.0000000000001045","article-title":"Visual outcomes in Leber hereditary optic neuropathy patients with the m.11778G>a (MTND4) mitochondrial DNA mutation","volume":"40","author":"Newman","year":"2020","journal-title":"J Neuroophthalmol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1097\/WNO.0000000000001564","article-title":"The impact of Leber hereditary optic neuropathy on the quality of life of patients and their relatives: a qualitative study","volume":"42","author":"Chen","year":"2022","journal-title":"J Neuroophthalmol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1007\/s00417-021-05534-0","article-title":"Capturing the experiences of patients with inherited optic neuropathies: a systematic review of patient-reported outcome measures (PROMs) and qualitative studies","volume":"260","author":"Chen","year":"2022","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1097\/WCO.0000000000001343","article-title":"Clinical trials in Leber hereditary optic neuropathy: outcomes and opportunities","volume":"38","author":"Chen","year":"2025","journal-title":"Curr Opin Neurol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1038\/s41433-021-01535-9","article-title":"Natural history of patients with Leber hereditary optic neuropathy-results from the REALITY study","volume":"36","author":"Yu-Wai-Man","year":"2022","journal-title":"Eye Lond Engl"},{"key":"ref13","first-page":"481","article-title":"Primary pathogenic mt DNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy","volume":"59","author":"Mackey","year":"1996","journal-title":"Am J Hum Genet"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"584","DOI":"10.3390\/biomedicines12030584","article-title":"The optic nerve at stake: update on environmental factors modulating expression of Leber\u2019s hereditary optic neuropathy","volume":"12","author":"Layrolle","year":"2024","journal-title":"Biomedicines"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.ajhg.2022.11.014","article-title":"Is the disease risk and penetrance in Leber hereditary optic neuropathy actually low?","volume":"110","author":"Mackey","year":"2023","journal-title":"Am J Hum Genet"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.tjo.2011.09.001","article-title":"Leber hereditary optic neuropathy \u2013 therapeutic challenges and early promise","volume":"1","author":"Yu-Wai-Man","year":"2011","journal-title":"Taiwan J Ophthalmol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"R245","DOI":"10.1093\/hmg\/ddab156","article-title":"Mitochondrial DNA disorders: from pathogenic variants to preventing transmission","volume":"30","author":"Bernardino Gomes","year":"2021","journal-title":"Hum Mol Genet"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.ajo.2005.11.007","article-title":"Influence of mutation type on clinical expression of Leber hereditary optic neuropathy","volume":"141","author":"Spruijt","year":"2006","journal-title":"Am J Ophthalmol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1136\/bjophthalmol-2016-310072","article-title":"Childhood-onset Leber hereditary optic neuropathy","volume":"101","author":"Majander","year":"2017","journal-title":"Br J Ophthalmol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1167\/iovs.08-2695","article-title":"Association of optic disc size with development and prognosis of Leber\u2019s hereditary optic neuropathy","volume":"50","author":"Ramos C do","year":"2009","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1097\/WNO.0000000000000830","article-title":"Clinical and optic disc characteristics of patients showing visual recovery in Leber hereditary optic neuropathy","volume":"40","author":"Moon","year":"2020","journal-title":"J Neuroophthalmol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/s10384-025-01185-4","article-title":"Remarkable visual improvement in Leber hereditary optic neuropathy","volume":"69","author":"Takai","year":"2025","journal-title":"Jpn J Ophthalmol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1016\/j.ophtha.2013.04.022","article-title":"Dominant optic atrophy\u2013novel OPA1 mutations and revised prevalence estimates","volume":"120","author":"Yu-Wai-Man","year":"2013","journal-title":"Ophthalmology"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.preteyeres.2010.11.002","article-title":"Mitochondrial optic neuropathies \u2013 disease mechanisms and therapeutic strategies","volume":"30","author":"Yu-Wai-Man","year":"2011","journal-title":"Prog Retin Eye Res"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/s11910-024-01343-0","article-title":"Maculopapillary bundle degeneration in optic neuropathies","volume":"24","author":"Lambiri","year":"2024","journal-title":"Curr Neurol Neurosci Rep"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1093\/brain\/awq007","article-title":"Multi-system neurological disease is common in patients with OPA1 mutations","volume":"133","author":"Yu-Wai-Man","year":"2010","journal-title":"Brain"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/S1474-4422(22)00174-0","article-title":"Understanding the molecular basis and pathogenesis of hereditary optic neuropathies: towards improved diagnosis and management","volume":"22","author":"Newman","year":"2023","journal-title":"Lancet Neurol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/s13023-019-1187-1","article-title":"OPA1: 516 unique variants and 831 patients registered in an updated centralized Variome database","volume":"14","author":"Le Roux","year":"2019","journal-title":"Orphanet J Rare Dis"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e0253987","DOI":"10.1371\/journal.pone.0253987","article-title":"Mutation spectrum of the OPA1 gene in a large cohort of patients with suspected dominant optic atrophy: identification and classification of 48 novel variants","volume":"16","author":"Weisschuh","year":"2021","journal-title":"PLoS One"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/s41586-023-06441-6","article-title":"Structural mechanism of mitochondrial membrane remodelling by human OPA1","volume":"620","author":"von der Malsburg","year":"2023","journal-title":"Nature"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.bbabio.2018.01.005","article-title":"Eight human OPA1 isoforms, long and short: what are they for?","volume":"1859","author":"Del Dotto","year":"2018","journal-title":"Biochim Biophys Acta"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/s41580-024-00785-1","article-title":"Molecular mechanisms of mitochondrial dynamics","volume":"26","author":"T\u00e1bara","year":"2025","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1002\/ana.21376","article-title":"Reversible optic neuropathy with OPA1 exon 5b mutation","volume":"63","author":"Cornille","year":"2008","journal-title":"Ann Neurol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"100935","DOI":"10.1016\/j.preteyeres.2020.100935","article-title":"Dominant optic atrophy: culprit mitochondria in the optic nerve","volume":"83","author":"Lenaers","year":"2021","journal-title":"Prog Retin Eye Res"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.4103\/IJO.IJO_594_24","article-title":"Recent advances in neuro-ophthalmology","volume":"72","author":"Bassi","year":"2024","journal-title":"Indian J Ophthalmol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"a041282","DOI":"10.1101\/cshperspect.a041282","article-title":"From bench to bedside-delivering gene therapy for Leber hereditary optic neuropathy","volume":"12","author":"Chen","year":"2022","journal-title":"Cold Spring Harb Perspect Med"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.ophtha.2020.12.012","article-title":"Efficacy and safety of intravitreal gene therapy for Leber hereditary optic neuropathy treated within 6 months of disease onset","volume":"128","author":"Newman","year":"2021","journal-title":"Ophthalmology"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"eaaz7423","DOI":"10.1126\/scitranslmed.aaz7423","article-title":"Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy","volume":"12","author":"Yu-Wai-Man","year":"2020","journal-title":"Sci Transl Med"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1093\/brain\/awac421","article-title":"LHON REFLECT Study Group. Randomized trial of bilateral gene therapy injection for m.11778G>A MTND4 Leber optic neuropathy","volume":"146","author":"Newman","year":"2023","journal-title":"Brain"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1097\/WNO.0000000000001367","article-title":"Long-term follow-up after unilateral intravitreal gene therapy for Leber hereditary optic neuropathy: the RESTORE study","volume":"41","author":"Biousse","year":"2021","journal-title":"J Neuroophthalmol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"7739","DOI":"10.1167\/iovs.14-15388","article-title":"LHON gene therapy vector prevents visual loss and optic neuropathy induced by G11778A mutant mitochondrial DNA: biodistribution and toxicology profile","volume":"55","author":"Koilkonda","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"21587","DOI":"10.1038\/srep21587","article-title":"Efficacy and safety of rAAV2-ND4 treatment for Leber\u2019s hereditary optic neuropathy","volume":"6","author":"Wan","year":"2016","journal-title":"Sci Rep"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1001\/jamaophthalmol.2013.7630","article-title":"Safety and effects of the vector for the Leber hereditary optic neuropathy gene therapy clinical trial","volume":"132","author":"Koilkonda","year":"2014","journal-title":"JAMA Ophthalmol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.ajo.2022.02.023","article-title":"Leber hereditary optic neuropathy gene therapy: adverse events and visual acuity results of all patient groups","volume":"241","author":"Lam","year":"2022","journal-title":"Am J Ophthalmol"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.ajo.2023.09.005","article-title":"Leber hereditary optic neuropathy gene therapy: longitudinal relationships among visual function and anatomical measures","volume":"257","author":"Lam","year":"2024","journal-title":"Am J Ophthalmol"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e730","DOI":"10.1111\/aos.14379","article-title":"Factors associated with rapid improvement in visual acuity in patients with Leber\u2019s hereditary optic neuropathy after gene therapy","volume":"98","author":"Liu","year":"2020","journal-title":"Acta Ophthalmol"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1111\/ceo.13515","article-title":"Prognostic factors for visual acuity in patients with Leber\u2019s hereditary optic neuropathy after rAAV2-ND4 gene therapy","volume":"47","author":"Zhang","year":"2019","journal-title":"Clin Experiment Ophthalmol"},{"key":"ref48","year":""},{"key":"ref49","doi-asserted-by":"publisher","first-page":"e230","DOI":"10.1093\/brain\/aws279","article-title":"Persistence of the treatment effect of idebenone in Leber\u2019s hereditary optic neuropathy","volume":"136","author":"Klopstock","year":"2013","journal-title":"Brain"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1097\/WNO.0000000000001023","article-title":"Real-world clinical experience with idebenone in the treatment of Leber hereditary optic neuropathy","volume":"40","author":"Catarino","year":"2020","journal-title":"J Neuroophthalmol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.1093\/brain\/awr170","article-title":"A randomized placebo-controlled trial of idebenone in Leber\u2019s hereditary optic neuropathy","volume":"134","author":"Klopstock","year":"2011","journal-title":"Brain"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"101437","DOI":"10.1016\/j.xcrm.2024.101437","article-title":"Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: the LEROS nonrandomized controlled trial","volume":"5","author":"Yu-Wai-Man","year":"2024","journal-title":"Cell Rep Med"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1093\/brain\/awae308","article-title":"Optimizing rare disorder trials: a phase 1a\/1b randomized study of KL1333 in adults with mitochondrial disease","volume":"148","author":"Pizzamiglio","year":"2025","journal-title":"Brain"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.3390\/biom12101411","article-title":"Modeling reactive oxygen species-induced axonal loss in Leber hereditary optic neuropathy","volume":"12","author":"Lambiri","year":"2022","journal-title":"Biomol Ther"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.mito.2018.07.007","article-title":"Toxic medications in Leber\u2019s hereditary optic neuropathy","volume":"46","author":"Kogachi","year":"2019","journal-title":"Mitochondrion"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1089\/nat.2024.0022","article-title":"Antisense oligonucleotide STK-002 increases OPA1 in retina and improves mitochondrial function in autosomal dominant optic atrophy cells","volume":"34","author":"Venkatesh","year":"2024","journal-title":"Nucleic Acid Ther"},{"key":"ref57","first-page":"5305","article-title":"PYC-001: a promising RNA therapeutic for autosomal dominant optic atrophy","volume":"65","author":"Grainok","year":"2024","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.2022.15427","article-title":"OPA1 trans-splicing: a gene therapy approach to treat OPA1-related optic neuropathies","volume":"100","author":"le Dantec","year":"2022","journal-title":"Acta Ophthalmol Copenh"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"e231","DOI":"10.1093\/brain\/aws280","article-title":"Idebenone treatment in patients with OPA1-mutant dominant optic atrophy","volume":"136","author":"Barboni","year":"2013","journal-title":"Brain J Neurol"},{"key":"ref60","doi-asserted-by":"publisher","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 Transl Neurol"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1080\/01658107.2023.2251575","article-title":"Idebenone treatment in patients with OPA1-dominant optic atrophy: a prospective phase 2 trial","volume":"47","author":"Valentin","year":"2023","journal-title":"Neuro Ophthalmol"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.exer.2014.08.012","article-title":"The effect of visual blue light on mitochondrial function associated with retinal ganglions cells","volume":"128","author":"Osborne","year":"2014","journal-title":"Exp Eye Res"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"109","DOI":"10.7150\/ijms.52980","article-title":"Near infrared (NIR) light therapy of eye diseases: a review","volume":"18","author":"Zhu","year":"2021","journal-title":"Int J Med Sci"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s40265-020-01428-3","article-title":"Therapeutic options in hereditary optic neuropathies","volume":"81","author":"Amore","year":"2021","journal-title":"Drugs"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/j.neuron.2019.11.006","article-title":"Single-cell profiles of retinal ganglion cells differing in resilience to injury reveal neuroprotective genes","volume":"104","author":"Tran","year":"2019","journal-title":"Neuron"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1111\/j.1471-4159.2008.05401.x","article-title":"Characterization of OPA1 isoforms isolated from mouse tissues","volume":"106","author":"Akepati","year":"2008","journal-title":"J Neurochem"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"165743","DOI":"10.1016\/j.bbadis.2020.165743","article-title":"Emerging model systems and treatment approaches for Leber\u2019s hereditary optic neuropathy: challenges and opportunities","volume":"1866","author":"Bahr","year":"2020","journal-title":"Biochim Biophys Acta Mol basis Dis"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.18632\/aging.101231","article-title":"Mitochondrial replacement in an iPSC model of Leber\u2019s hereditary optic neuropathy","volume":"9","author":"Wong","year":"2017","journal-title":"Aging"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s40478-025-01942-z","article-title":"Disruption of mitochondrial homeostasis and permeability transition pore opening in OPA1 iPSC-derived retinal ganglion cells","volume":"13","author":"Whitehead","year":"2025","journal-title":"Acta Neuropathol Commun"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.omtn.2021.08.015","article-title":"CRISPR-Cas 9 correction of OPA1 c.1334G>A: p.R445H restores mitochondrial homeostasis in dominant optic atrophy patient-derived iPSCs","volume":"26","author":"Sladen","year":"2021","journal-title":"Mol Ther Nucleic Acids"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.omtn.2023.02.032","article-title":"Efficient correction of ABCA4 variants by CRISPR-Cas 9 in hi PSCs derived from Stargardt disease patients","volume":"32","author":"Siles","year":"2023","journal-title":"Mol Ther"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13024-023-00655-y","article-title":"Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe consortium","volume":"18","author":"Soucy","year":"2023","journal-title":"Mol Neurodegener"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"2750","DOI":"10.3390\/biomedicines12122750","article-title":"Revolutionizing personalized medicine: synergy with multi-omics data generation, main hurdles, and future perspectives","volume":"12","author":"Molla","year":"2024","journal-title":"Biomedicines"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"147","DOI":"10.3390\/genes12020147","article-title":"From transcriptomics to treatment in inherited optic neuropathies","volume":"12","author":"Gilhooley","year":"2021","journal-title":"Genes"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/nrg.2016.10","article-title":"Translating RNA sequencing into clinical diagnostics: opportunities and challenges","volume":"17","author":"Byron","year":"2016","journal-title":"Nat Rev Genet"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"950","DOI":"10.3892\/ijmm.2015.2103","article-title":"Characterization of three alternative transcripts of the BRCA1 gene in patients with breast cancer and a family history of breast and\/or ovarian cancer who tested negative for pathogenic mutations","volume":"35","author":"Gambino","year":"2015","journal-title":"Int J Mol Med"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13073-022-01075-1","article-title":"An introduction to spatial transcriptomics for biomedical research","volume":"14","author":"Williams","year":"2022","journal-title":"Genome Med"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/nbt0118-6a","article-title":"FDA approves hereditary blindness gene therapy","volume":"36","year":"2018","journal-title":"Nat Biotechnol"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"E1238","DOI":"10.1073\/pnas.1119577109","article-title":"Gene delivery to mitochondria by targeting modified adenoassociated virus suppresses Leber\u2019s hereditary optic neuropathy in a mouse model","volume":"109","author":"Yu","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1167\/tvst.9.11.1","article-title":"Mitochondrial transfer of the mutant human ND6T14484C gene causes visual loss and optic neuropathy","volume":"9","author":"Yu","year":"2020","journal-title":"Transl Vis Sci Technol"},{"key":"ref81","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.1093\/brain\/awad131","article-title":"Autosomal recessive Leber hereditary optic neuropathy, a new neuro-ophthalmo-genetic paradigm","volume":"146","author":"Lenaers","year":"2023","journal-title":"Brain"},{"key":"ref82","doi-asserted-by":"publisher","first-page":"4935","DOI":"10.1172\/JCI134965","article-title":"PRICKLE3 linked to ATPase biogenesis manifested Leber\u2019s hereditary optic neuropathy","volume":"130","author":"Yu","year":"2020","journal-title":"J Clin Invest"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"105308","DOI":"10.1016\/j.isci.2022.105308","article-title":"Transplanted human induced pluripotent stem cells- derived retinal ganglion cells embed within mouse retinas and are electrophysiologically functional","volume":"25","author":"Vrathasha","year":"2022","journal-title":"iScience"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3390\/bioengineering11010052","article-title":"Hereditary optic neuropathies: a systematic review on the interplay between biomaterials and induced pluripotent stem cells","volume":"11","author":"Ladero","year":"2024","journal-title":"Bioengineering"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1007\/s10237-021-01433-9","article-title":"Mechanical homeostasis in tissue equivalents: a review","volume":"20","author":"Eichinger","year":"2021","journal-title":"Biomech Model Mechanobiol"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/nbt.4114","article-title":"Phase 1 clinical study of an embryonic stem cell\u2013derived retinal pigment epithelium patch in age-related macular degeneration","volume":"36","author":"da Cruz","year":"2018","journal-title":"Nat Biotechnol"},{"key":"ref87","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/s41586-020-2477-4","article-title":"A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing","volume":"583","author":"Mok","year":"2020","journal-title":"Nature"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.cell.2015.03.051","article-title":"Selective elimination of mitochondrial mutations in the germline by genome editing","volume":"161","author":"Reddy","year":"2015","journal-title":"Cell"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"7804","DOI":"10.1093\/nar\/gkw676","article-title":"Near-complete elimination of mutant mt DNA by iterative or dynamic dose-controlled treatment with mtZFNs","volume":"44","author":"Gammage","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"3210","DOI":"10.1038\/s41467-021-23561-7","article-title":"Mitochondrial targeted meganuclease as a platform to eliminate mutant mt DNA in vivo","volume":"12","author":"Zekonyte","year":"2021","journal-title":"Nat Commun"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/7108948","article-title":"Progress in gene therapy to prevent retinal ganglion cell loss in glaucoma and Leber\u2019s hereditary optic neuropathy","volume":"2018","author":"Ratican","year":"2018","journal-title":"Neural Plast"},{"key":"ref92","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1080\/02713683.2019.1663385","article-title":"Neuroprotection in glaucoma: towards clinical trials and precision medicine","volume":"45","author":"Khatib","year":"2020","journal-title":"Curr Eye Res"},{"key":"ref93","doi-asserted-by":"publisher","first-page":"1536452","DOI":"10.3389\/fncel.2025.1536452","article-title":"The role of neurotrophic factors in retinal ganglion cell resiliency","volume":"19","author":"Abraham","year":"2025","journal-title":"Front Cell Neurosci"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"5614","DOI":"10.1038\/s41467-020-19436-y","article-title":"Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS","volume":"11","author":"Petrova","year":"2020","journal-title":"Nat Commun"},{"key":"ref95","doi-asserted-by":"publisher","first-page":"917348","DOI":"10.3389\/fnins.2022.917348","article-title":"Superoxide dismutase 2 ameliorates mitochondrial dysfunction in skin fibroblasts of Leber\u2019s hereditary optic neuropathy patients","volume":"16","author":"Zhou","year":"2022","journal-title":"Front Neurosci"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.3390\/biomedicines12092020","article-title":"Preservation of mitochondrial function by SkQ1 in skin fibroblasts derived from patients with Leber\u2019s hereditary optic neuropathy is associated with the PINK1\/PRKN-mediated mitophagy","volume":"12","author":"Xu","year":"2024","journal-title":"Biomedicines"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/s41431-018-0235-y","article-title":"Clinical utility gene card for: inherited optic neuropathies including next-generation sequencing-based approaches","volume":"27","author":"Jurkute","year":"2019","journal-title":"Eur J Hum Genet"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1609033\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T05:25:38Z","timestamp":1753421138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1609033\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,25]]},"references-count":97,"alternative-id":["10.3389\/fneur.2025.1609033"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1609033","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,25]]},"article-number":"1609033"}}