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Many ocular disorders have a mitochondrial involvement from primary mitochondrial disorders such as Leber hereditary optic neuropathy (LHON), predominantly due to mutations in genes encoding subunits of complex I, to Mendelian and multifactorial ocular conditions such as dominant optic atrophy, glaucoma and age-related macular degeneration. In this study, we have optimised the nuclear yeast gene, NADH-quinone oxidoreductase (NDI1), which encodes a single subunit complex I equivalent, creating a candidate gene therapy to improve mitochondrial function, independent of the genetic mutation driving disease. Optimisation of NDI1 (ophNdi1) substantially increased expression in vivo, protected RGCs and increased visual function, as assessed by optokinetic and photonegative response, in a rotenone-induced murine model. In addition, ophNdi1 increased cellular oxidative phosphorylation and ATP production and protected cells from rotenone insult to a significantly greater extent than wild type NDI1. Significantly, ophNdi1 treatment of complex I deficient patient-derived fibroblasts increased oxygen consumption and ATP production rates, demonstrating the potential of ophNdi1 as a candidate therapy for ocular disorders where mitochondrial deficits comprise an important feature.<\/jats:p>","DOI":"10.3390\/pharmaceutics15020322","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T03:45:16Z","timestamp":1674099916000},"page":"322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Optimisation of AAV-NDI1 Significantly Enhances Its Therapeutic Value for Correcting Retinal Mitochondrial Dysfunction"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1684-1598","authenticated-orcid":false,"given":"Naomi","family":"Chadderton","sequence":"first","affiliation":[{"name":"Department of Genetics, The School of Genetics and Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpad","family":"Palfi","sequence":"additional","affiliation":[{"name":"Department of Genetics, The School of Genetics and Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Maloney","sequence":"additional","affiliation":[{"name":"Department of Genetics, The School of Genetics and Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Carrigan","sequence":"additional","affiliation":[{"name":"Department of Genetics, The School of Genetics and Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3395-1211","authenticated-orcid":false,"given":"Laura K.","family":"Finnegan","sequence":"additional","affiliation":[{"name":"Department of Genetics, The School of Genetics and Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3957-6061","authenticated-orcid":false,"given":"Killian S.","family":"Hanlon","sequence":"additional","affiliation":[{"name":"Department of Genetics, The School of Genetics and Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciara","family":"Shortall","sequence":"additional","affiliation":[{"name":"Department of Genetics, The School of Genetics and Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"O\u2019Reilly","sequence":"additional","affiliation":[{"name":"Department of Genetics, The School of Genetics and Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Humphries","sequence":"additional","affiliation":[{"name":"Department of Genetics, The School of Genetics and Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Cassidy","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Royal Victoria Eye and Ear Hospital, D02 XK51 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Kenna","sequence":"additional","affiliation":[{"name":"Department of Genetics, The School of Genetics and Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"},{"name":"The Research Foundation, Royal Victoria Eye and Ear Hospital, D02 XK51 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Millington-Ward","sequence":"additional","affiliation":[{"name":"Department of Genetics, The School of Genetics and Microbiology, Trinity College Dublin, D02 VF25 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.bbadis.2009.07.012","article-title":"Mitochondria in Huntington\u2019s disease","volume":"1802","author":"Damiano","year":"2010","journal-title":"Biochim. Biophys. Acta BBA Mol. Basis Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"571479","DOI":"10.3389\/fnins.2020.571479","article-title":"Optimized OPA1 Isoforms 1 and 7 Provide Therapeutic Benefit in Models of Mitochondrial Dysfunction","volume":"14","author":"Maloney","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"784987","DOI":"10.3389\/fnins.2021.784987","article-title":"The Role of Mitochondria in Optic Atrophy With Autosomal Inheritance","volume":"15","author":"Strachan","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1086\/346066","article-title":"The Epidemiology of Leber Hereditary Optic Neuropathy in the North East of England","volume":"72","author":"Man","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1167\/iovs.05-1639","article-title":"Mitochondrial Abnormalities in Patients with Primary Open-Angle Glaucoma","volume":"47","author":"Morales","year":"2006","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dammak, A., Huete-Toral, F., Carpena-Torres, C., Martin-Gil, A., Pastrana, C., and Carracedo, G. (2021). From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13091376"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1007\/s00125-009-1655-6","article-title":"Neurodegenerative influence of oxidative stress in the retina of a murine model of diabetes","volume":"53","author":"Sasaki","year":"2010","journal-title":"Diabetologia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101799","DOI":"10.1016\/j.redox.2020.101799","article-title":"Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications","volume":"37","author":"Kang","year":"2020","journal-title":"Redox Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.redox.2017.05.015","article-title":"Altered bioenergetics and enhanced resistance to oxidative stress in human retinal pigment epithelial cells from donors with age-related macular degeneration","volume":"13","author":"Ferrington","year":"2017","journal-title":"Redox Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100858","DOI":"10.1016\/j.preteyeres.2020.100858","article-title":"Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration","volume":"79","author":"Kaarniranta","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1136\/bjo.84.3.303","article-title":"Retinal ganglion cell death in experimental glaucoma","volume":"84","author":"Morgan","year":"2000","journal-title":"Br. J. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","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":"ref_15","doi-asserted-by":"crossref","first-page":"661938","DOI":"10.3389\/fneur.2021.661938","article-title":"Retinal Ganglion Cells-Diversity of Cell Types and Clinical Relevance","volume":"12","author":"Kim","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1136\/bjo.83.2.231","article-title":"Histochemical localisation of mitochondrial enzyme activity in human optic nerve and retina","volume":"83","author":"Andrews","year":"1999","journal-title":"Br. J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1001\/archopht.120.6.791","article-title":"The Distribution of Mitochondrial Activity in Relation to Optic Nerve Structure","volume":"120","author":"Bristow","year":"2002","journal-title":"Arch. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.survophthal.2009.10.002","article-title":"The Neuro-ophthalmology of Mitochondrial Disease","volume":"55","author":"Fraser","year":"2010","journal-title":"J. Surv. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.4103\/1673-5374.272577","article-title":"Diabetic retinopathy: A matter of retinal ganglion cell homeostasis","volume":"15","author":"Catalani","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_20","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":"ref_21","doi-asserted-by":"crossref","first-page":"5742832","DOI":"10.1155\/2020\/5742832","article-title":"Outcome of Selective Laser Trabeculoplasty in Young Patients with Primary Open-Angle Glaucoma and Ocular Hypertension","volume":"2020","author":"Liu","year":"2020","journal-title":"J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1167\/iovs.15-18306","article-title":"Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population","volume":"57","author":"Rosenberg","year":"2016","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/sj.ejhg.5201828","article-title":"Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland","volume":"15","author":"Puomila","year":"2007","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_24","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":"ref_25","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1007\/s12325-018-0776-z","article-title":"Current and Emerging Treatment Modalities for Leber\u2019s Hereditary Optic Neuropathy: A Review of the Literature","volume":"35","author":"Karampitianis","year":"2018","journal-title":"Adv. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.4103\/ijo.IJO_358_17","article-title":"Mitochondrial genetics and therapeutic overview of Leber\u2019s hereditary optic neuropathy","volume":"65","author":"Manickam","year":"2017","journal-title":"Indian J. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1093\/hmg\/10.13.1369","article-title":"Spectrum, frequency and penetrance of OPA1 mutations in dominant optic atrophy","volume":"10","author":"Toomes","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","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":"Newman","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Almind, G.J., Ek, J., Rosenberg, T., Eiberg, H., Larsen, M., LuCamp, L., Br\u00f8ndum-Nielsen, K., and Gr\u00f8nskov, K. (2012). Dominant optic atrophy in Denmark\u2014Report of 15 novel mutations in OPA1, using a strategy with a detection rate of 90%. BMC Med. Genet., 13.","DOI":"10.1186\/1471-2350-13-65"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.bbrc.2016.10.134","article-title":"Imbalance of mitochondrial dynamics in Drosophila models of amyotrophic lateral sclerosis","volume":"481","author":"Altanbyek","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e50973","DOI":"10.7554\/eLife.50973","article-title":"Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane","volume":"9","author":"Ge","year":"2020","journal-title":"eLife"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"626117","DOI":"10.3389\/fcell.2021.626117","article-title":"Mitochondrial OMA1 and OPA1 as Gatekeepers of Organellar Structure\/Function and Cellular Stress Response","volume":"9","author":"Gilkerson","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13762","DOI":"10.1038\/s41598-021-92971-w","article-title":"Prevalence of primary open angle glaucoma in the last 20 years: A meta-analysis and systematic review","volume":"11","author":"Zhang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_34","first-page":"e11686","article-title":"Epidemiology of Glaucoma: The Past, Present, and Predictions for the Future","volume":"12","author":"Allison","year":"2020","journal-title":"Cureus"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ejphar.2016.04.032","article-title":"Glaucoma: Focus on mitochondria in relation to pathogenesis and neuroprotection","volume":"787","author":"Osborne","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Van Bergen, N.J., Crowston, J.G., Craig, J.E., Burdon, K.P., Kearns, L.S., Sharma, S., Hewitt, A.W., Mackey, D.A., and Trounce, I.A. (2015). Measurement of Systemic Mitochondrial Function in Advanced Primary Open-Angle Glaucoma and Leber Hereditary Optic Neuropathy. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140919"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e138267","DOI":"10.1172\/JCI138267","article-title":"Impaired complex I repair causes recessive Leber\u2019s hereditary optic neuropathy","volume":"131","author":"Stenton","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Marella, M., Seo, B.B., Thomas, B.B., Matsuno-Yagi, A., and Yagi, T. (2010). Successful Amelioration of Mitochondrial Optic Neuropathy Using the Yeast NDI1 Gene in a Rat Animal Model. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011472"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/ejhg.2012.112","article-title":"Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy","volume":"21","author":"Chadderton","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1007\/s12035-019-01857-6","article-title":"Gene Therapy with Single-Subunit Yeast NADH-Ubiquinone Oxidoreductase (NDI1) Improves the Visual Function in Experimental Autoimmune Encephalomyelitis (EAE) Mice Model of Multiple Sclerosis (MS)","volume":"57","author":"Talla","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_41","first-page":"428370","article-title":"Protective Role of rAAV-NDI1, Serotype 5, in an Acute MPTP Mouse Parkinson\u2019s Model","volume":"2011","author":"Seo","year":"2011","journal-title":"Park. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.omtm.2017.11.007","article-title":"Emerging Issues in AAV-Mediated In Vivo Gene Therapy","volume":"8","author":"Colella","year":"2017","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3389\/fimmu.2017.00278","article-title":"The Immune Epitope Database and Analysis Resource in Epitope Discovery and Synthetic Vaccine Design","volume":"8","author":"Fleri","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"D913","DOI":"10.1093\/nar\/gkq1128","article-title":"Allele frequency net: A database and online repository for immune gene frequencies in worldwide populations","volume":"39","author":"Christmas","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10915","DOI":"10.1073\/pnas.89.22.10915","article-title":"Amino acid substitution matrices from protein blocks","volume":"89","author":"Henikoff","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/mt.2008.227","article-title":"Undetectable Transcription of cap in a Clinical AAV Vector: Implications for Preformed Capsid in Immune Responses","volume":"17","author":"Hauck","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"891","DOI":"10.3389\/fnins.2020.00891","article-title":"AAV-Delivered Tulp1Supplementation Therapy Targeting Photoreceptors Provides Minimal Benefit in Tulp1-\/- Retinas","volume":"14","author":"Palfi","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/nprot.2012.058","article-title":"Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells","volume":"7","author":"Spinazzi","year":"2012","journal-title":"Nat. Protoc."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Finnegan, L.K., Chadderton, N., Kenna, P.F., Palfi, A., Carty, M., Bowie, A.G., Millington-Ward, S., and Farrar, G.J. (2022). SARM1 Ablation Is Protective and Preserves Spatial Vision in an In Vivo Mouse Model of Retinal Ganglion Cell Degeneration. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031606"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1086\/519025","article-title":"RNA Interference-Mediated Suppression and Replacement of Human Rhodopsin In Vivo","volume":"81","author":"Palfi","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/sj.mt.6300389","article-title":"Reversal of Blindness in Animal Models of Leber Congenital Amaurosis Using Optimized AAV2-mediated Gene Transfer","volume":"16","author":"Bennicelli","year":"2008","journal-title":"Mol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0166-0934(02)00138-6","article-title":"Fast and reliable titration of recombinant adeno-associated virus type-2 using quantitative real-time PCR","volume":"106","author":"Rohr","year":"2002","journal-title":"J. Virol. Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/mt.2010.293","article-title":"Suppression and Replacement Gene Therapy for Autosomal Dominant Disease in a Murine Model of Dominant Retinitis Pigmentosa","volume":"19","author":"Chadderton","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15016","DOI":"10.1038\/mtm.2015.16","article-title":"Efficient gene delivery to photoreceptors using AAV2\/rh10 and rescue of the Rho(-\/-) mouse","volume":"2","author":"Palfi","year":"2015","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/mt.2008.301","article-title":"Improved Retinal Function in a Mouse Model of Dominant Retinitis Pigmentosa Following AAV-delivered Gene Therapy","volume":"17","author":"Chadderton","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4611","DOI":"10.1167\/iovs.04-0541","article-title":"Rapid Quantification of Adult and Developing Mouse Spatial Vision Using a Virtual Optomotor System","volume":"45","author":"Prusky","year":"2004","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1017\/S0952523805225166","article-title":"Independent visual threshold measurements in the two eyes of freely moving rats and mice using a virtual-reality optokinetic system","volume":"22","author":"Douglas","year":"2005","journal-title":"Vis. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"31431","DOI":"10.1038\/srep31431","article-title":"microRNA regulatory circuits in a mouse model of inherited retinal degeneration","volume":"6","author":"Palfi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3860","DOI":"10.1167\/iovs.08-3267","article-title":"Brn3a as a Marker of Retinal Ganglion Cells: Qualitative and Quantitative Time Course Studies in Naive and Optic Nerve-Injured Retinas","volume":"50","author":"Agudo","year":"2009","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.exer.2015.05.010","article-title":"Time-dependent retinal ganglion cell loss, microglial activation and blood-retina-barrier tightness in an acute model of ocular hypertension","volume":"136","author":"Trost","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7193","DOI":"10.1523\/JNEUROSCI.16-22-07193.1996","article-title":"Genetic and Environmental Control of Variation in Retinal Ganglion Cell Number in Mice","volume":"16","author":"Williams","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"16515","DOI":"10.1038\/s41598-020-73257-z","article-title":"Novel 199 base pair NEFH promoter drives expression in retinal ganglion cells","volume":"10","author":"Chadderton","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_63","unstructured":"Farrar, G.J., Millington-Ward, S., Chadderton, N., Carrigan, M.A., and Kenna, P. (2019). Variants of Yeast NDI1 Gene, and Uses Thereof in the Treatment of Disease Associated with Mitochondrial Dysfunction. (US20150099798A1), US Patent."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9167","DOI":"10.1073\/pnas.95.16.9167","article-title":"Molecular remedy of complex I defects: Rotenone-insensitive internal NADH-quinone oxidoreductase of Saccharomyces cerevisiae mitochondria restores the NADH oxidase activity of complex I-deficient mammalian cells","volume":"95","author":"Seo","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"37774","DOI":"10.1074\/jbc.M007033200","article-title":"Use of the NADH-Quinone Oxidoreductase (NDI1) Gene ofSaccharomyces cerevisiae as a Possible Cure for Complex I Defects in Human Cells","volume":"275","author":"Seo","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"38808","DOI":"10.1074\/jbc.M106363200","article-title":"Lack of complex I activity in human cells carrying a mutation in MtDNA-encoded ND4 subunit is corrected by the Saccharomyces cerevisiae NADH-quinone oxidoreductase (NDI1) gene","volume":"276","author":"Bai","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Cronin-Furman, E.N., Barber-Singh, J., Bergquist, K.E., Yagi, T., and Trimmer, P.A. (2019). Differential Effects of Yeast NADH Dehydrogenase (Ndi1) Expression on Mitochondrial Function and Inclusion Formation in a Cell Culture Model of Sporadic Parkinson\u2019s Disease. Biomolecules, 9.","DOI":"10.3390\/biom9040119"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.bbabio.2008.11.003","article-title":"Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species","volume":"1787","author":"Fato","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"45465","DOI":"10.1038\/srep45465","article-title":"Mechanistic Investigations of the Mitochondrial Complex I Inhibitor Rotenone in the Context of Pharmacological and Safety Evaluation","volume":"7","author":"Heinz","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0304-3940(02)00327-0","article-title":"Mouse model of optic neuropathy caused by mitochondrial complex I dysfunction","volume":"326","author":"Zhang","year":"2002","journal-title":"Neurosci. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1080\/15287390600630203","article-title":"Neurodegeneration Produced by Rotenone in the Mouse Retina: A Potential Model to Investigate Environmental Pesticide Contributions to Neurodegenerative Diseases","volume":"69","author":"Zhang","year":"2006","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1080\/15287390802414190","article-title":"Transgenic Mice Expressing Cyan Fluorescent Protein as a Reporter Strain to Detect the Effects of Rotenone Toxicity on Retinal Ganglion Cells","volume":"71","author":"Hayworth","year":"2008","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.mito.2017.01.004","article-title":"Evaluating the therapeutic potential of idebenone and related quinone analogues in Leber hereditary optic neuropathy","volume":"36","author":"Soiferman","year":"2017","journal-title":"Mitochondrion"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1038\/s41598-020-58505-6","article-title":"Fibroblast mitochondria in idiopathic Parkinson\u2019s disease display morphological changes and enhanced resistance to depolarization","volume":"10","author":"Antony","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e952","DOI":"10.1002\/ctm2.952","article-title":"AAV-mediated gene therapy improving mitochondrial function provides benefit in age-related macular degeneration models","volume":"12","author":"Chadderton","year":"2022","journal-title":"Clin. Transl. Med."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Marella, M., Seo, B.B., Nakamaru-Ogiso, E., Greenamyre, J.T., Matsuno-Yagi, A., and Yagi, T. (2008). Protection by the NDI1 gene against neurodegeneration in a rotenone rat model of Parkinson\u2019s disease. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001433"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.ymthe.2020.01.001","article-title":"Immune Responses to Viral Gene Therapy Vectors","volume":"28","author":"Shirley","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/mt.2010.258","article-title":"Preclinical Safety Evaluation of AAV2-sFLT01\u2014A Gene Therapy for Age-related Macular Degeneration","volume":"19","author":"MacLachlan","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_79","first-page":"16011","article-title":"Ocular and systemic safety of a recombinant AAV8 vector for X-linked retinoschisis gene therapy: GLP studies in rabbits and Rs1-KO mice","volume":"5","author":"Marangoni","year":"2014","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1089\/humc.2015.164","article-title":"Safety and Biodistribution Evaluation in Cynomolgus Macaques of rAAV2tYF-PR1.7-hCNGB3, a Recombinant AAV Vector for Treatment of Achromatopsia","volume":"27","author":"Ye","year":"2016","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/j.ymthe.2020.07.009","article-title":"Broader Implications of Progressive Liver Dysfunction and Lethal Sepsis in Two Boys following Systemic High-Dose AAV","volume":"28","author":"Morales","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_82","unstructured":"Adverum Biotechnologies, Inc. (2022, June 20). Update on ADVM-022 and INFINITY Trial 07\/22\/201. Available online: https:\/\/investors.adverum.com\/news\/news-details\/2021\/Adverum-Provides-Update-on-ADVM-022-and-the-INFINITY-Trial-in-Patients-with-Diabetic-Macular-Edema\/default.aspx."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"S350","DOI":"10.1016\/j.gim.2022.01.568","article-title":"OP018: ASPIRO gene therapy trial in X-Linked Myotubular Myopathy (XLMTM): Update on preliminary efficacy and safety findings","volume":"24","author":"Shieh","year":"2022","journal-title":"Genet. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/B978-0-12-802395-2.00010-9","article-title":"Mitochondrial diseases","volume":"145","author":"Molnar","year":"2017","journal-title":"Handb. Clin. Neurol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"De Barcelos, I.P., Troxell, R.M., and Graves, J.S. (2019). Mitochondrial Dysfunction and Multiple Sclerosis. Biology, 8.","DOI":"10.3390\/biology8020037"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1038\/sj.gt.3303029","article-title":"Systemic AAV-9 transduction in mice is influenced by animal age but not by the route of administration","volume":"14","author":"Bostick","year":"2007","journal-title":"Gene Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nbt.1515","article-title":"Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes","volume":"27","author":"Foust","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/gt.2011.163","article-title":"Enhanced gene delivery to the neonatal retina through systemic administration of tyrosine-mutated AAV9","volume":"19","author":"Dalkara","year":"2012","journal-title":"Gene Ther."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.omtm.2019.10.007","article-title":"Selection of an Efficient AAV Vector for Robust CNS Transgene Expression","volume":"15","author":"Hanlon","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1038\/nn.4593","article-title":"Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems","volume":"20","author":"Chan","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41434-018-0028-5","article-title":"More expansive gene transfer to the rat CNS: AAV PHP.EB vector dose\u2013response and comparison to AAV PHP.B","volume":"25","author":"Dayton","year":"2018","journal-title":"Gene Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1093\/brain\/awaa105","article-title":"Gene replacement therapy provides benefit in an adult mouse model of Leigh syndrome","volume":"143","author":"Benegiamo","year":"2020","journal-title":"Brain"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.omtm.2022.03.016","article-title":"AAV-PHP.eB transduces both the inner and outer retina with high efficacy in mice","volume":"25","author":"Palfi","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41593-021-00969-4","article-title":"AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset","volume":"25","author":"Goertsen","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","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":"ref_97","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1177\/1120672120936592","article-title":"Treatment of Leber\u2019s hereditary optic neuropathy: An overview of recent developments","volume":"30","author":"Zuccarelli","year":"2020","journal-title":"Eur. J. Ophthalmol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"624","DOI":"10.2174\/1381612823666170125164856","article-title":"Treatment of Leber\u2019s Hereditary Optic Neuropathy","volume":"23","author":"Sadun","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_99","doi-asserted-by":"crossref","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":"ref_100","doi-asserted-by":"crossref","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":"ref_101","doi-asserted-by":"crossref","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. Neuro Ophthalmol."},{"key":"ref_102","doi-asserted-by":"crossref","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":"ref_103","doi-asserted-by":"crossref","first-page":"P661","DOI":"10.1016\/j.ophtha.2021.01.023","article-title":"Gene Therapy for Leber Hereditary Optic Neuropathy: Is Vision Truly RESCUED?","volume":"128","author":"Chen","year":"2021","journal-title":"Ophthalmology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/s41433-021-01535-9","article-title":"Natural history of patients with Leber hereditary optic neuropathy\u2014Results from the REALITY study","volume":"36","author":"Newman","year":"2022","journal-title":"Eye"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/2\/322\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:09:23Z","timestamp":1760119763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/2\/322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":104,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["pharmaceutics15020322"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15020322","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]}}}