{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:46:50Z","timestamp":1789991210037,"version":"4.0.1"},"reference-count":119,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2012,9,4]],"date-time":"2012-09-04T00:00:00Z","timestamp":1346716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2012,9,4]],"date-time":"2012-09-04T00:00:00Z","timestamp":1346716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Neurol"],"published-print":{"date-parts":[[2012,10]]},"DOI":"10.1038\/nrneurol.2012.167","type":"journal-article","created":{"date-parts":[[2012,9,4]],"date-time":"2012-09-04T10:57:39Z","timestamp":1346756259000},"page":"545-556","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Treatment of hereditary optic neuropathies"],"prefix":"10.1038","volume":"8","author":[{"given":"Nancy J.","family":"Newman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,9,4]]},"reference":[{"key":"BFnrneurol2012167_CR1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.preteyeres.2003.10.003","volume":"23","author":"V Carelli","year":"2004","unstructured":"Carelli, V., Ross-Cisneros, F. N. & Sadun, A. A. Mitochondrial dysfunction as a cause of optic neuropathies. Prog. Retin. Eye Res. 23, 53\u201389 (2004).","journal-title":"Prog. Retin. Eye Res."},{"key":"BFnrneurol2012167_CR2","first-page":"465","volume-title":"Walsh & Hoyt's Clinical Neuro-Ophthalmology","author":"NJ Newman","year":"2005","unstructured":"Newman, N. J. in Walsh & Hoyt's Clinical Neuro-Ophthalmology 6th edn (eds Miller, N. R.  et al.) 465\u2013501 (Williams & Willkins, Baltimore, 2005)."},{"key":"BFnrneurol2012167_CR3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1136\/jmg.2007.054270","volume":"46","author":"P Yu-Wai-Man","year":"2009","unstructured":"Yu-Wai-Man, P., Griffiths, P. G., Hudson, G. & Chinnery, P. F. Inherited optic neuropathies. J. Med. Genet. 46, 145\u2013158 (2009).","journal-title":"J. Med. Genet."},{"key":"BFnrneurol2012167_CR4","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.survophthal.2009.10.002","volume":"55","author":"JA Fraser","year":"2010","unstructured":"Fraser, J. A., Newman, N. J. & Biousse, V. The neuro-ophthalmology of mitochondrial disease. Surv. Ophthalmol. 55, 299\u2013334 (2010).","journal-title":"Surv. Ophthalmol."},{"key":"BFnrneurol2012167_CR5","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.preteyeres.2010.11.002","volume":"30","author":"P Yu-Wai-Man","year":"2011","unstructured":"Yu-Wai-Man, P., Griffiths, P. G. & Chinnery, P. F. Mitochondrial optic neuropathies\u2014disease mechanisms and therapeutic strategies. Prog. Retin. Eye Res. 30, 81\u2013114 (2011).","journal-title":"Prog. Retin. Eye Res."},{"key":"BFnrneurol2012167_CR6","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1007\/s11910-012-0260-0","volume":"12","author":"KS Sitarz","year":"2012","unstructured":"Sitarz, K. S., Chinnery, P. F. & Yu-Wai-Man, P. Disorders of the optic nerve in mitochondrial cytopathies: new ideas on pathogenesis and therapeutic targets. Curr. Neurol. Neurosci. Rep. 12, 308\u2013317 (2012).","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"BFnrneurol2012167_CR7","unstructured":"Biousse, V. B. & Newman, N. J. in Pediatric Ophthalmology 4th edn (eds Taylor, D. & Hoyt, C. S.) Elsevier Saunders, London [in press]."},{"key":"BFnrneurol2012167_CR8","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1016\/S0002-9394(14)76784-4","volume":"111","author":"NJ Newman","year":"1991","unstructured":"Newman, N. J., Lott, M. T. & Wallace, D. C. The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. Am. J. Ophthalmol. 111, 750\u2013762 (1991).","journal-title":"Am. J. Ophthalmol."},{"key":"BFnrneurol2012167_CR9","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1093\/brain\/118.2.319","volume":"118","author":"P Riordan-Eva","year":"1995","unstructured":"Riordan-Eva, P.  et al. The clinical features of Leber's hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain 118, 319\u2013337 (1995).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR10","first-page":"407","volume":"140","author":"NJ Newman","year":"2005","unstructured":"Newman, N. J.  et al. Prophylaxis for second eye involvement in Leber hereditary optic neuropathy: an open-labeled, nonrandomized multicenter trial of topical brimonidine purite. Am. J. Ophthalmol. 140, 407\u2013415 (2005).","journal-title":"Am. J. Ophthalmol."},{"key":"BFnrneurol2012167_CR11","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/S0161-6420(96)30665-9","volume":"103","author":"EK Nikoskelainen","year":"1996","unstructured":"Nikoskelainen, E. K.  et al. Ophthalmoscopic findings in Leber hereditary optic neuropathy, with special reference to mtDNA mutations. Ophthalmology 103, 504\u2013514 (1996).","journal-title":"Ophthalmology"},{"key":"BFnrneurol2012167_CR12","first-page":"1218","volume":"51","author":"D Mackey","year":"1992","unstructured":"Mackey, D. & Howell, N. A variant of Leber's hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology. Am. J. Hum. Genet. 51, 1218\u20131228 (1992).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrneurol2012167_CR13","first-page":"10","volume":"12","author":"EM Stone","year":"1992","unstructured":"Stone, E. M.  et al. Visual recovery in patients with Leber's hereditary optic neuropathy and the 11778 mutation. J. Clin. Neuroophthalmol. 12, 10\u201314 (1992).","journal-title":"J. Clin. Neuroophthalmol."},{"key":"BFnrneurol2012167_CR14","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1136\/jmg.31.4.280","volume":"31","author":"RJ Oostra","year":"1994","unstructured":"Oostra, R. J.  et al. Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome. J. Med. Genet. 31, 280\u2013286 (1994).","journal-title":"J. Med. Genet."},{"key":"BFnrneurol2012167_CR15","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/j.ajo.2005.11.007","volume":"141","author":"L Spruijt","year":"2006","unstructured":"Spruijt, L.  et al. Influence of mutation type on clinical expression of Leber hereditary optic neuropathy. Am. J. Ophthalmol. 141, 676\u2013682 (2006).","journal-title":"Am. J. Ophthalmol."},{"key":"BFnrneurol2012167_CR16","doi-asserted-by":"publisher","first-page":"e188","DOI":"10.1093\/brain\/awr180","volume":"134","author":"V Carelli","year":"2011","unstructured":"Carelli, V.  et al. Idebenone treatment in Leber's hereditary optic neuropathy. Brain 134, e188 (2011).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR17","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1001\/archopht.1992.01080230077025","volume":"110","author":"DR Johns","year":"1992","unstructured":"Johns, D. R., Smith, K. H. & Miller, N. R. Leber's hereditary optic neuropathy: clinical manifestations of the 3460 mutation. Arch. Ophthalmol. 110, 1577\u20131581 (1992).","journal-title":"Arch. Ophthalmol."},{"key":"BFnrneurol2012167_CR18","first-page":"1063","volume":"55","author":"B Obermaier-Kusser","year":"1994","unstructured":"Obermaier-Kusser, B.  et al. Features of mtDNA mutation patterns in European pedigrees and sporadic cases with Leber hereditary optic neuropathy. Am. J. Hum. Genet. 55, 1063\u20131066 (1994).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrneurol2012167_CR19","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.ophtha.2004.06.034","volume":"112","author":"P Barboni","year":"2005","unstructured":"Barboni, P.  et al. Retinal nerve fiber layer evaluation by optical coherence tomography in Leber's hereditary optic neuropathy. Ophthalmology 112, 120\u2013126 (2005).","journal-title":"Ophthalmology"},{"key":"BFnrneurol2012167_CR20","doi-asserted-by":"publisher","first-page":"5303","DOI":"10.1167\/iovs.06-0520","volume":"47","author":"P Barboni","year":"2006","unstructured":"Barboni, P.  et al. Leber's hereditary optic neuropathy with childhood onset. Invest. Ophthalmol. Vis. Sci. 47, 5303\u20135309 (2006).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"BFnrneurol2012167_CR21","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1167\/iovs.08-2695","volume":"50","author":"V Ramos Cdo","year":"2009","unstructured":"Ramos Cdo, V.  et al. Association of optic disc size with development and prognosis of Leber's hereditary optic neuropathy. Invest. Ophthalmol. Vis. Sci. 50, 1666\u20131674 (2009).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"BFnrneurol2012167_CR22","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S0161-6420(80)35247-0","volume":"87","author":"CS Hoyt","year":"1980","unstructured":"Hoyt, C. S. Autosomal dominant optic atrophy\u2014a spectrum of disability. Ophthalmology 87, 245\u2013251 (1980).","journal-title":"Ophthalmology"},{"key":"BFnrneurol2012167_CR23","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1136\/bjo.2007.134726","volume":"92","author":"AC Cohn","year":"2008","unstructured":"Cohn, A. C.  et al. The natural history of OPA1-related autosomal dominant optic atrophy. Br. J. Ophthalmol. 92, 1333\u20131336 (2008).","journal-title":"Br. J. Ophthalmol."},{"key":"BFnrneurol2012167_CR24","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/S0161-6420(99)90013-1","volume":"106","author":"RL Johnson","year":"1999","unstructured":"Johnson, R. L.  et al. Dominant optic atrophy. Refining the clinical diagnostic criteria in light of genetic linkage studies. Ophthalmology 106, 123\u2013128 (1999).","journal-title":"Ophthalmology"},{"key":"BFnrneurol2012167_CR25","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.ajo.2006.12.038","volume":"143","author":"AC Cohn","year":"2007","unstructured":"Cohn, A. C.  et al. Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations. Am. J. Ophthalmol. 143, 656\u2013662 (2007).","journal-title":"Am. J. Ophthalmol."},{"key":"BFnrneurol2012167_CR26","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1600-0420.1996.tb00672.x","volume":"74","author":"B Kjer","year":"1996","unstructured":"Kjer, B.  et al. Dominant optic atrophy mapped to chromosome 3q region. II. Clinical and epidemiological aspects. Acta Ophthalmol. Scand. 74, 3\u20137 (1996).","journal-title":"Acta Ophthalmol. Scand."},{"key":"BFnrneurol2012167_CR27","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1001\/archopht.116.3.351","volume":"116","author":"M Votruba","year":"1998","unstructured":"Votruba, M.  et al. Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy. Arch. Ophthalmol. 116, 351\u2013358 (1998).","journal-title":"Arch. Ophthalmol."},{"issue":"Suppl. 54","key":"BFnrneurol2012167_CR28","first-page":"1","volume":"164","author":"P Kjer","year":"1959","unstructured":"Kjer, P. Infantile optic atrophy with dominant mode of inheritance. A clinical and genetic study of 19 Danish families. Acta Ophthalmol. 164 (Suppl. 54), 1\u2013147 (1959).","journal-title":"Acta Ophthalmol."},{"key":"BFnrneurol2012167_CR29","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/S0002-9394(14)73589-5","volume":"115","author":"D Eliott","year":"1993","unstructured":"Eliott, D., Traboulsi, E. I. & Maumenee, I. H. Visual prognosis in autosomal dominant optic atrophy (Kjer type). Am. J. Ophthalmol. 115, 360\u2013367 (1993).","journal-title":"Am. J. Ophthalmol."},{"key":"BFnrneurol2012167_CR30","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1111\/j.1600-0420.2005.00448.x","volume":"83","author":"A Puomila","year":"2005","unstructured":"Puomila, A.  et al. Dominant optic atrophy: correlation between clinical and molecular genetic studies. Acta Ophthalmol. Scand. 83, 337\u2013346 (2005).","journal-title":"Acta Ophthalmol. Scand."},{"key":"BFnrneurol2012167_CR31","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1016\/j.ophtha.2009.12.038","volume":"117","author":"P Yu-Wai-Man","year":"2010","unstructured":"Yu-Wai-Man, P.  et al. The prevalence and natural history of dominant optic atrophy due to OPA1 mutations. Ophthalmology 117, 1538\u20131546 (2010).","journal-title":"Ophthalmology"},{"key":"BFnrneurol2012167_CR32","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1002\/ana.21376","volume":"63","author":"K Cornille","year":"2008","unstructured":"Cornille, K.  et al. Reversible optic neuropathy with OPA1 exon 5b mutation. Ann. Neurol. 63, 667\u2013671 (2008).","journal-title":"Ann. Neurol."},{"key":"BFnrneurol2012167_CR33","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1093\/brain\/awq007","volume":"133","author":"P Yu-Wai-Man","year":"2010","unstructured":"Yu-Wai-Man, P.  et al. Multi-system neurological disease is common in patients with OPA1 mutations. Brain 133, 771\u2013786 (2010).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR34","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1038\/eye.2011.2","volume":"25","author":"P Yu-Wai-Man","year":"2011","unstructured":"Yu-Wai-Man, P.  et al. Pattern of retinal ganglion cell loss in dominant optic atrophy due to OPA1 mutations. Eye 25, 596\u2013602, (2011).","journal-title":"Eye"},{"key":"BFnrneurol2012167_CR35","doi-asserted-by":"publisher","first-page":"e4492","DOI":"10.1371\/journal.pone.0004492","volume":"4","author":"S Tang","year":"2009","unstructured":"Tang, S.  et al. Heterozygous mutation of Opa1 in Drosophila shortens lifespan mediated through increased reactive oxygen species production. PLoS ONE 4, e4492 (2009).","journal-title":"PLoS ONE"},{"key":"BFnrneurol2012167_CR36","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1212\/WNL.39.4.595","volume":"39","author":"H Costeff","year":"1989","unstructured":"Costeff, H.  et al. A familial syndrome of infantile optic atrophy, movement disorder, and spastic paraplegia. Neurology 39, 595\u2013597 (1989).","journal-title":"Neurology"},{"key":"BFnrneurol2012167_CR37","doi-asserted-by":"publisher","first-page":"2839","DOI":"10.1007\/s00018-010-0365-z","volume":"67","author":"SW Ryu","year":"2010","unstructured":"Ryu, S. W.  et al. Optic atrophy 3 as a protein of the mitochondrial outer membrane induces mitochondrial fragmentation. Cell. Mol. Life Sci. 67, 2839\u20132850 (2010).","journal-title":"Cell. Mol. Life Sci."},{"key":"BFnrneurol2012167_CR38","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.ajhg.2009.03.003","volume":"84","author":"S Hanein","year":"2009","unstructured":"Hanein, S.  et al. TMEM126A, encoding a mitochondrial protein, is mutated in autosomal-recessive nonsyndromic optic atrophy. Am. J. Hum. Genet. 84, 493\u2013498 (2009).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrneurol2012167_CR39","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.cell.2010.02.026","volume":"141","author":"HC Chen","year":"2010","unstructured":"Chen, H. C.  et al. Mitochondrial fusion is required for mtDNA stability in skeletqal muscle and tolerance of mtDNA mutations. Cell 141, 280\u2013289 (2010).","journal-title":"Cell"},{"key":"BFnrneurol2012167_CR40","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1101\/gr.108696.110","volume":"21","author":"G Elachouri","year":"2011","unstructured":"Elachouri, G.  et al. OPA1 links human mitochondrial genome maintenance to mtDNA replication and distribution. Genome Res. 21, 12\u201320 (2011).","journal-title":"Genome Res."},{"key":"BFnrneurol2012167_CR41","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3109\/13816811003698117","volume":"31","author":"G Dayanithi","year":"2010","unstructured":"Dayanithi, G.  et al. Characterization of Ca2+ signaling in postnatal mouse retinal ganglioin cells: involvement of OPA1 in Ca2+ clearance. Ophthalmic Genet. 31, 53\u201365 (2010).","journal-title":"Ophthalmic Genet."},{"key":"BFnrneurol2012167_CR42","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/nature07534","volume":"456","author":"OM de Brito","year":"2008","unstructured":"de Brito, O. M. & Scorrano, L. Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456, 605\u2013610 (2008).","journal-title":"Nature"},{"key":"BFnrneurol2012167_CR43","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1093\/brain\/awq023","volume":"133","author":"AJ Trevelyan","year":"2010","unstructured":"Trevelyan, A. J.  et al. Mitochondrial DNA mutations affect calcium handling in differentiated neurons. Brain 133, 787\u2013796 (2010).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR44","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/S0092-8674(00)81203-9","volume":"93","author":"G Casari","year":"1998","unstructured":"Casari, G.  et al. Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell 93, 973\u2013983 (1998).","journal-title":"Cell"},{"key":"BFnrneurol2012167_CR45","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1093\/brain\/awn269","volume":"132","author":"F Fortuna","year":"2009","unstructured":"Fortuna, F.  et al., Visual system involvement in patients with Friedreichs ataxia. Brain 132, 116\u2013123 (2009).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR46","doi-asserted-by":"publisher","first-page":"26737","DOI":"10.1074\/jbc.R110.118679","volume":"285","author":"TL Stemmler","year":"2010","unstructured":"Stemmler, T. L.  et al. Frataxin and mitochondrial FeS cluster biogenesis. J. Biol. Chem. 285, 26737\u201326743 (2010).","journal-title":"J. Biol. Chem."},{"key":"BFnrneurol2012167_CR47","doi-asserted-by":"publisher","unstructured":"Pfeffer, G., Majaama, K., Turnbull, D. M., Thorburn, D. & Chinnery, P. F. Treatment for mitochondrial disorders. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD004426. http:\/\/dx.doi.org\/10.1002\/14651858.CD004426.pub3.","DOI":"10.1002\/14651858.CD004426.pub3"},{"key":"BFnrneurol2012167_CR48","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s10540-007-9041-4","volume":"27","author":"S DiMauro","year":"2007","unstructured":"DiMauro, S. & Mancuso, M. Mitochondrial diseases: therapeutic approaches. Biosci. Rep. 27, 125\u2013137 (2007).","journal-title":"Biosci. Rep."},{"key":"BFnrneurol2012167_CR49","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1212\/WNL.38.6.892","volume":"38","author":"N Bresolin","year":"1988","unstructured":"Bresolin, N.  et al. Clinical and biochemical correlations in mitochondrial myopathies treated with coenzyme Q10 . Neurology 38, 392\u2013399 (1988).","journal-title":"Neurology"},{"key":"BFnrneurol2012167_CR50","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/0022-510X(90)90015-F","volume":"100","author":"N Bresolin","year":"1990","unstructured":"Bresolin, N.  et al. Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial. J. Neurol. Sci. 100, 70\u201378 (1990).","journal-title":"J. Neurol. Sci."},{"key":"BFnrneurol2012167_CR51","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S1096-7192(02)00145-2","volume":"77","author":"V Geromel","year":"2002","unstructured":"Geromel, V.  et al. Coenzyme Q10 and idebenone in the therapy of respiratory chain diseases: rationale and comparative benefits. Mol. Genet. Metab. 77, 21\u201330 (2002).","journal-title":"Mol. Genet. Metab."},{"key":"BFnrneurol2012167_CR52","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1212\/WNL.57.3.515","volume":"57","author":"S Di Giovanni","year":"2001","unstructured":"Di Giovanni, S.  et al. Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency. Neurology 57, 515\u2013518 (2001).","journal-title":"Neurology"},{"key":"BFnrneurol2012167_CR53","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1097\/00041327-200203000-00036","volume":"22","author":"CC Huang","year":"2002","unstructured":"Huang, C. C., Kuo, H. C., Chu, C. C. & Kao, L. Y. Rapid visual recovery after coenzyme Q10 treatment of Leber hereditary optic neuropathy. J. Neuroophthalmol. 22, 66 (2002).","journal-title":"J. Neuroophthalmol."},{"key":"BFnrneurol2012167_CR54","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1093\/brain\/awm135","volume":"130","author":"RK Olsen","year":"2007","unstructured":"Olsen, R. K.  et al. ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Brain 130, 2045\u20132054 (2007).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR55","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1203\/00006450-199009000-00020","volume":"28","author":"I Tein","year":"1990","unstructured":"Tein, I.  et al. Impaired skin fibroblast carnitine uptake in primary systemic carnitine deficiency manifested by childhood carnitine-responsive cardiomyopathy. Pediatr. Res. 28, 247\u2013255 (1990).","journal-title":"Pediatr. Res."},{"key":"BFnrneurol2012167_CR56","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1002\/mus.20688","volume":"35","author":"MC Rodriguez","year":"2007","unstructured":"Rodriguez, M. C.  et al. Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders. Muscle Nerve 35, 235\u2013242 (2007).","journal-title":"Muscle Nerve"},{"key":"BFnrneurol2012167_CR57","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1016\/j.addr.2008.05.001","volume":"60","author":"MA Tarnopolsky","year":"2008","unstructured":"Tarnopolsky, M. A. The mitochondrial cocktail: rationale for combined nutraceutical therapy in mitochondrial cytopathies. Adv. Drug Deliv. Rev. 60, 1561\u20131567 (2008).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"BFnrneurol2012167_CR58","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.bbabio.2011.10.012","volume":"1817","author":"V Giorgio","year":"2012","unstructured":"Giorgio, V.  et al. The effects of idebenone on mitochondrial bioenergetics. Biochim. Biophys. Acta 1817, 363\u2013369 (2012).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnrneurol2012167_CR59","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1186\/1756-0500-4-557","volume":"4","author":"C Angebault","year":"2011","unstructured":"Angebault, C.  et al. Idebenone increases mitochondrial complex I activity in fibroblasts from LHON patients while producing contradictory effects on respiration. BMC Res. Notes 4, 557 (2011).","journal-title":"BMC Res. Notes"},{"key":"BFnrneurol2012167_CR60","doi-asserted-by":"publisher","first-page":"e17963","DOI":"10.1371\/journal.pone.0017963","volume":"6","author":"RH Haefeli","year":"2011","unstructured":"Haefeli, R. H.  et al. NQO1-dependent redox cycling of idebenone: effects on cellular redox potential and energy levels. PLoS ONE 6, e17963 (2011).","journal-title":"PLoS ONE"},{"key":"BFnrneurol2012167_CR61","doi-asserted-by":"publisher","first-page":"1676","DOI":"10.1212\/01.WNL.0000055872.50364.FC","volume":"60","author":"C Mariotti","year":"2003","unstructured":"Mariotti, C.  et al. Idebenone treatment in Friedreich patients: one-year-long randomized placebo-controlled trial. Neurology 60, 1676\u20131679 (2003).","journal-title":"Neurology"},{"key":"BFnrneurol2012167_CR62","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1016\/S1474-4422(07)70220-X","volume":"6","author":"NA Di Prospero","year":"2007","unstructured":"Di Prospero, N. A., Baker, A., Jeffries, N. & Fishbeck, K. H. Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomized, placebo-controlled trial. Lancet Neurol. 6, 878\u2013886 (2007).","journal-title":"Lancet Neurol."},{"key":"BFnrneurol2012167_CR63","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1001\/archneurol.2010.168","volume":"67","author":"DR Lynch","year":"2010","unstructured":"Lynch, D. R., Perlman, S. L. & Meier, T. A phase 3, double-blind, placebo-controlled trial of idebenone in Friedreich ataxia. Arch. Neurol. 67, 941\u2013947 (2010).","journal-title":"Arch. Neurol."},{"key":"BFnrneurol2012167_CR64","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.ahj.2010.10.038","volume":"161","author":"SJ Lagedrost","year":"2011","unstructured":"Lagedrost, S. J.  et al. Idebenone in Friedreich ataxia cardiomyopathy\u2014results from a 6-month phase III study (IONIA). Am. Heart J. 161, 639\u2013645 (2011).","journal-title":"Am. Heart J."},{"key":"BFnrneurol2012167_CR65","first-page":"209","volume":"21","author":"J Imachi","year":"1970","unstructured":"Imachi, J. & Nishizaki, K. The patients of Leber's optic atrophy should be treated neuro-surgically [Japanese]. Nihon Ganka Kiyo 21, 209\u2013217 (1970).","journal-title":"Nihon Ganka Kiyo"},{"key":"BFnrneurol2012167_CR66","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.nbd.2007.07.021","volume":"28","author":"MF Haroon","year":"2007","unstructured":"Haroon, M. F.  et al. Minocycline, a possible neuroprotective agent in Leber's hereditary optic neuropathy (LHON): studies of cybrid cells bearing 11778 mutation. Neurobiol. Dis. 28, 237\u2013250 (2007).","journal-title":"Neurobiol. Dis."},{"key":"BFnrneurol2012167_CR67","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1006\/bbrc.1997.7443","volume":"239","author":"A Wong","year":"1997","unstructured":"Wong, A. & Cortopassi, G. mtDNA mutations confer cellular sensitivity to oxidant stress that is partially rescued by calcium depletion and cyclosporine A. Biochem. Biophys. Res. Commun. 239, 139\u2013145 (1997).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"BFnrneurol2012167_CR68","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/S0006-8993(98)00790-2","volume":"809","author":"TA Seaton","year":"1998","unstructured":"Seaton, T. A., Cooper, J. M. & Schapira, A. H. Cyclosporin inhibition of apoptosis by mitochondrial complex I toxins. Brain Res. 809, 12\u201317 (1998).","journal-title":"Brain Res."},{"key":"BFnrneurol2012167_CR69","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1074\/jbc.M807321200","volume":"284","author":"AM Porcelli","year":"2009","unstructured":"Porcelli, A. M.  et al. Respiratory complex I dysfunction due to mitochondrial DNA mutations shifts the voltage threshold for opening of the permeability transition pore toward resting levels. J. Biol. Chem. 284, 2045\u20132052 (2009).","journal-title":"J. Biol. Chem."},{"key":"BFnrneurol2012167_CR70","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1167\/iovs.07-0880","volume":"49","author":"A Ghelli","year":"2008","unstructured":"Ghelli, A.  et al. Protection against oxidant-induced apoptosis by exogenous glutathione in Leber hereditary optic neuropathy cybrids. Invest. Ophthalmol. Vis. Sci. 49, 671\u2013676 (2008).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"BFnrneurol2012167_CR71","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1086\/498176","volume":"77","author":"G Hudson","year":"2005","unstructured":"Hudson, G.  et al. Identification of an X-chromosome locus and haplotype modulating the phenotype of a mitochondrial DNA disorder. Am. J. Hum. Genet. 77, 1086\u20131091 (2005).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrneurol2012167_CR72","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1080\/13816810701867607","volume":"29","author":"SP Shankar","year":"2008","unstructured":"Shankar, S. P.  et al. Evidence for a novel X-linked modifier locus for Leber hereditary optic neuropathy. Ophthalmic Genet. 29, 17\u201324 (2008).","journal-title":"Ophthalmic Genet."},{"key":"BFnrneurol2012167_CR73","first-page":"416","volume":"16","author":"YL Ji","year":"2010","unstructured":"Ji, Y. L.  et al. Evaluation of the X-linked modifier loci for Leber hereditary optic neuropathy with the G11778A mutation in Chinese. Mol. Vis. 16, 416\u2013424 (2010).","journal-title":"Mol. Vis."},{"key":"BFnrneurol2012167_CR74","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1093\/brain\/awq276","volume":"134","author":"C Giordano","year":"2011","unstructured":"Giordano, C.  et al. Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy. Brain 134, 220\u2013234 (2011).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR75","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/0140-6736(92)91442-B","volume":"340","author":"Y Mashima","year":"1992","unstructured":"Mashima, Y., Hiida, Y. & Oguchi, Y. Remission of Leber's hereditary optic neuropathy with idebenone. Lancet 340, 368\u2013369 (1992).","journal-title":"Lancet"},{"key":"BFnrneurol2012167_CR76","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S0022-510X(96)00311-5","volume":"148","author":"P Cortelli","year":"1997","unstructured":"Cortelli, P.  et al. Clinical and brain bioenergetics improvement with idebenone in a patient with Leber hereditary optic neuropathy: a clinical and P-MRS study. J. Neurol. Sci. 148, 25\u201331 (1997).","journal-title":"J. Neurol. Sci."},{"key":"BFnrneurol2012167_CR77","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/S0022-510X(98)00239-1","volume":"160","author":"V Carelli","year":"1998","unstructured":"Carelli, V.  et al. Leber's hereditary optic neuroapathy (LHON) with 14484\/ND6 mutation in a North African patient. J. Neurol. Sci. 160, 183\u2013188 (1998).","journal-title":"J. Neurol. Sci."},{"key":"BFnrneurol2012167_CR78","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1097\/00041327-200020030-00006","volume":"20","author":"Y Mashima","year":"2000","unstructured":"Mashima, Y., Kigasawa, K., Wakakura, M. & Oguchi, Y. Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy? J. Neuroophthalmol. 20, 166\u2013170 (2000).","journal-title":"J. Neuroophthalmol."},{"key":"BFnrneurol2012167_CR79","doi-asserted-by":"publisher","first-page":"377","DOI":"10.4321\/S0365-66912007000600012","volume":"82","author":"N Barnils","year":"2007","unstructured":"Barnils, N., Mesa, E., Munoz, S., Ferrer-Artola, A. & Arruga, J. Response to idebenone and multivitamin therapy in Leber's hereditary optic neuropathy [Spanish]. Arch. Soc. Esp. Oftalmol. 82, 377\u2013380 (2007).","journal-title":"Arch. Soc. Esp. Oftalmol."},{"key":"BFnrneurol2012167_CR80","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.1093\/brain\/awr170","volume":"134","author":"K Klopstock","year":"2011","unstructured":"Klopstock, K.  et al. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain 134, 2677\u20132686 (2011).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR81","doi-asserted-by":"publisher","first-page":"2447","DOI":"10.1093\/brain\/awr192","volume":"134","author":"NJ Newman","year":"2011","unstructured":"Newman, N. J. Treatment of Leber hereditary optic neuropathy. Brain 134, 2447\u20132450 (2011).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR82","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1001\/archneurol.2011.2972","volume":"69","author":"AA Sadun","year":"2012","unstructured":"Sadun, A. A.  et al. Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy. Arch. Neurol. 69, 331\u2013338 (2012).","journal-title":"Arch. Neurol."},{"key":"BFnrneurol2012167_CR83","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s10540-007-9041-4","volume":"27","author":"S DiMauro","year":"2007","unstructured":"DiMauro, S. & Mancuso, M. Mitochondrial diseases: therapeutic approaches. Biosci. Rep. 27, 125\u2013137 (2007).","journal-title":"Biosci. Rep."},{"key":"BFnrneurol2012167_CR84","doi-asserted-by":"publisher","first-page":"179412","DOI":"10.1155\/2011\/179412","volume":"2011","author":"RD Koilkonda","year":"2011","unstructured":"Koilkonda, R. D. & Guy, J. Leber's hereditary optic neuropathy-gene therapy: from benchtop to bedside. J. Ophthalmol. 2011, 179412 (2011).","journal-title":"J. Ophthalmol."},{"key":"BFnrneurol2012167_CR85","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1093\/brain\/awr290","volume":"135","author":"A Bouaita","year":"2012","unstructured":"Bouaita, A.  et al. Downregulation of apoptosis-inducing factor in Harlequin mice induces progressive and severe optic atrophy which is durably prevented by AAV2\u2013AIF1 gene therapy. Brain 135, 35\u201352 (2012).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR86","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/S1525-0016(03)00037-6","volume":"7","author":"A Flierl","year":"2003","unstructured":"Flierl, A.  et al. Targeted delivery of DNA to the mitochondrial compartment via import sequence-conjugated peptide nucleic acid. Mol. Ther. 7, 550\u2013557 (2003).","journal-title":"Mol. Ther."},{"key":"BFnrneurol2012167_CR87","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1002\/ana.10354","volume":"52","author":"J Guy","year":"2002","unstructured":"Guy, J.  et al. Rescue of a mitochondrial deficiency causing Leber hereditary optic neuropathy. Ann. Neurol. 52, 534\u20134270 (2002).","journal-title":"Ann. Neurol."},{"key":"BFnrneurol2012167_CR88","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/ng851","volume":"30","author":"G Manfredi","year":"2002","unstructured":"Manfredi, G.  et al. Rescue of an ATP synthesis deficiency in mtDNA-mutant human cells by transfer of MTATP6, a mtDNA-encoded gene, to the nucleus. Nat. Genet. 30, 394\u2013399 (2002).","journal-title":"Nat. Genet."},{"key":"BFnrneurol2012167_CR89","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1089\/rej.2006.0526","volume":"10","author":"C Bonnet","year":"2007","unstructured":"Bonnet, C.  et al. Allotopic mRNA localization to the mitochondrial surface rescues respiratory chain defects in fibroblasts harboring mitochondrial DNA mutations affecting complex I or V subunits. Rejuvenation Res. 10, 127\u2013144 (2007).","journal-title":"Rejuvenation Res."},{"key":"BFnrneurol2012167_CR90","doi-asserted-by":"publisher","first-page":"e11472","DOI":"10.1371\/journal.pone.0011472","volume":"5","author":"M Marella","year":"2010","unstructured":"Marella, M., Seo, B. B., Thomas, B. B., Matsuno-Yagi, A. & Yagi, T. Successful amelioration of mitochondrial optic neuropathy using the yeast NDI1 gene in a rat animal model. PLoS ONE 5, e11472 (2010).","journal-title":"PLoS ONE"},{"key":"BFnrneurol2012167_CR91","doi-asserted-by":"publisher","first-page":"4205","DOI":"10.1167\/iovs.08-3214","volume":"50","author":"J Guy","year":"2009","unstructured":"Guy, J.  et al. Efficiency and safety of AAV mediated gene delivery of the human ND4 complex I subunit in the mouse visual system. Invest. Ophthalmol. Vis. Sci. 50, 4205\u20134214 (2009).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"BFnrneurol2012167_CR92","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1167\/iovs.06-0789","volume":"48","author":"X Qi","year":"2007","unstructured":"Qi, X., Sun, L., Lewin, A. S., Hauswirth, W. W. & Guy, J. The mutant human ND4 subunit of complex I induces optic neuropathy in the mouse. Invest. Ophthalmol. Vis. Sci. 48, 1\u201310 (2007).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"BFnrneurol2012167_CR93","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.ajhg.2008.08.013","volume":"83","author":"S Ellouze","year":"2008","unstructured":"Ellouze, S.  et al. Optimized allotropic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction. Am. J. Hum. Genet. 83, 373\u2013387 (2008).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrneurol2012167_CR94","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1111\/j.1742-4658.2004.04542.x","volume":"272","author":"M Floreani","year":"2005","unstructured":"Floreani, M.  et al. Antioxidant defences in cybrids harboring mtDNA mutations associated with Leber's hereditary optic neuropathy. FEBS J. 272, 1124\u20131135 (2005).","journal-title":"FEBS J."},{"key":"BFnrneurol2012167_CR95","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1001\/archopht.125.2.268","volume":"125","author":"X Qi","year":"2007","unstructured":"Qi, X.  et al. Use of mitochondrial antioxidant defenses for rescue of cells with a Leber hereditary optic neuropathy-causing mutation. Arch. Ophthalmol. 125, 268\u2013272 (2007).","journal-title":"Arch. Ophthalmol."},{"key":"BFnrneurol2012167_CR96","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1002\/ana.20175","volume":"56","author":"X Qi","year":"2004","unstructured":"Qi, X.  et al. SOD2 gene transfer protects against optic neuropathy induced by deficiency of complex I. Ann. Neurol. 56, 182\u2013191 (2004).","journal-title":"Ann. Neurol."},{"key":"BFnrneurol2012167_CR97","first-page":"E1238","volume":"109","author":"H Yu","year":"2012","unstructured":"Yu, H.  et al. Gene delivery to mitochondria by targeting modified adenoassociated virus suppresses Leber's hereditary optic neuropathy in a mouse model. Proc. Natl Acad. Sci. USA 109, E1238\u2013E1247 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnrneurol2012167_CR98","first-page":"534","volume":"9","author":"M Tanaka","year":"2002","unstructured":"Tanaka, M.  et al. Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria. J. Biomed. Sci. 9, 534\u2013541 (2002).","journal-title":"J. Biomed. Sci."},{"key":"BFnrneurol2012167_CR99","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1038\/sj.gt.3302981","volume":"14","author":"SR Bacman","year":"2007","unstructured":"Bacman, S. R.  et al. Modulating mtDNA heteroplasmy by mitochondria-targeted restriction endonucleases in a 'differential multiple cleavage-site' model. Gene Ther. 14, 1309\u20131318 (2007).","journal-title":"Gene Ther."},{"key":"BFnrneurol2012167_CR100","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1002\/1096-8628(20010122)98:3<235::AID-AJMG1086>3.0.CO;2-O","volume":"98","author":"PF Chinnery","year":"2001","unstructured":"Chinnery, P. F., Andrews, R. M., Turnbull, D. M. & Howell, N. N. Leber hereditary optic neuropathy: does heteroplasmy influence the inheritance and expression of the G11778A mitochondrial DNA mutation? Am. J. Med. Genet. 98, 235\u2013243 (2001).","journal-title":"Am. J. Med. Genet."},{"key":"BFnrneurol2012167_CR101","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/nature08368","volume":"461","author":"M Tachibana","year":"2009","unstructured":"Tachibana, M.  et al. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature 461, 367\u2013372 (2009).","journal-title":"Nature"},{"key":"BFnrneurol2012167_CR102","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/nature08958","volume":"465","author":"L Craven","year":"2010","unstructured":"Craven, L.  et al. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature 465, 82\u201385 (2010).","journal-title":"Nature"},{"key":"BFnrneurol2012167_CR103","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1001\/archophthalmol.2010.201","volume":"128","author":"BJ Lam","year":"2010","unstructured":"Lam, B. J.  et al. Leber hereditary optic neuropathy gene therapy clinical trial recruitment: year 1. Arch. Ophthalmol. 128, 1129\u20131135 (2010).","journal-title":"Arch. Ophthalmol."},{"key":"BFnrneurol2012167_CR104","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1093\/nar\/gkq769","volume":"39","author":"E Perales-Clemente","year":"2011","unstructured":"Perales-Clemente, E.  et al. Allotopic expression of mitochondrial-encoded genes in mammals: achieved goal, undemonstrated mechanism or impossible task? Nucleic Acids Res. 39, 225\u2013234 (2011).","journal-title":"Nucleic Acids Res."},{"key":"BFnrneurol2012167_CR105","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.mito.2010.09.003","volume":"11","author":"F Figueroa-Martinez","year":"2011","unstructured":"Figueroa-Martinez, F.  et al. What limits the allotropic expression of nucleus-encoded mitochondrial genes? The case of the chimeric Cox3 and Atp6 genes. Mitochondrion 11, 147\u2013154 (2011).","journal-title":"Mitochondrion"},{"key":"BFnrneurol2012167_CR106","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1038\/gt.2008.91","volume":"15","author":"DS Kyriakouli","year":"2008","unstructured":"Kyriakouli, D. S.  et al. Progress and prospects: gene therapy for mitochondrial DNA disease. Gene Ther. 15, 1017\u20131023 (2008).","journal-title":"Gene Ther."},{"key":"BFnrneurol2012167_CR107","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1001\/archopht.126.5.608","volume":"126","author":"JA Stelmack","year":"2008","unstructured":"Stelmack, J. A.  et al. Outcomes of the Veterans Affairs Low Vision Intervention Trial (LOVIT). Arch. Ophthalmol. 126, 608\u2013617 (2008).","journal-title":"Arch. Ophthalmol."},{"key":"BFnrneurol2012167_CR108","doi-asserted-by":"publisher","first-page":"3112","DOI":"10.1167\/iovs.08-3166","volume":"50","author":"MA Kirkman","year":"2009","unstructured":"Kirkman, M. A.  et al. Quality of life in patients with Leber hereditary optic neuropathy. Invest. Ophthalmol. Vis. Sci. 50, 3112\u20133115 (2009).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"BFnrneurol2012167_CR109","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1093\/brain\/awp158","volume":"132","author":"M Kirkman","year":"2009","unstructured":"Kirkman, M.  et al. Gene-environment interactions in Leber hereditary optic neuropathy. Brain 132, 2317\u20132326 (2009).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR110","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1093\/brain\/awp195","volume":"132","author":"NJ Newman","year":"2009","unstructured":"Newman, N. J. Leber hereditary optic neuropathy: bad habits, bad vision? Brain 132, 2306\u20132308 (2009).","journal-title":"Brain"},{"key":"BFnrneurol2012167_CR111","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1093\/hmg\/10.13.1369","volume":"10","author":"C Toomes","year":"2001","unstructured":"Toomes, C.  et al. Spectrum, frequency, and penetrance of OPA1 mutations in dominant optic atrophy. Hum. Mol. Genet. 10, 1369\u20131378 (2001).","journal-title":"Hum. Mol. Genet."},{"key":"BFnrneurol2012167_CR112","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/S0140-6736(06)68972-1","volume":"368","author":"DT Brown","year":"2006","unstructured":"Brown, D. T.  et al. Transmission of mitochondrial DNA disorders: possibilities for the future. Lancet 368, 87\u201389 (2006).","journal-title":"Lancet"},{"key":"BFnrneurol2012167_CR113","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1034\/j.1600-0420.2002.800108.x","volume":"80","author":"K Huoponen","year":"2002","unstructured":"Huoponen, K.  et al. Genetic counseling in Leber hereditary optic neuropathy (LHON). Acta Ophthalmol. Scand. 80, 38\u201343 (2002).","journal-title":"Acta Ophthalmol. Scand."},{"key":"BFnrneurol2012167_CR114","first-page":"77","volume":"57","author":"AE Harding","year":"1995","unstructured":"Harding, A. E., Sweeney, M. G., Govan, G. G. & Riordan-Eva, P. Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation. Am. J. Hum. Genet. 57, 77\u201386 (1995).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrneurol2012167_CR115","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1212\/WNL.50.2.417","volume":"50","author":"C Macmillan","year":"1998","unstructured":"Macmillan, C.  et al. Pedigree analysis of French Canadian families with T14484C Leber's hereditary optic neuropathy. Neurology 50, 417\u2013422 (1998).","journal-title":"Neurology"},{"key":"BFnrneurol2012167_CR116","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1086\/346066","volume":"72","author":"PY Man","year":"2003","unstructured":"Man, P. Y.  et al. The epidemiology of Leber hereditary optic neuropathy in the North East of England. Am. J. Hum. Genet. 72, 339\u2013339 (2003).","journal-title":"Am. J. Hum. Genet."},{"key":"BFnrneurol2012167_CR117","first-page":"115","volume":"2","author":"EK Nikoskelainen","year":"1994","unstructured":"Nikoskelainen, E. K. Clinical picture of LHON. Clin. Neurosci. 2, 115\u2013120 (1994).","journal-title":"Clin. Neurosci."},{"key":"BFnrneurol2012167_CR118","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1111\/j.1442-9071.1992.tb00937.x","volume":"20","author":"DA Mackey","year":"1992","unstructured":"Mackey, D. A. & Buttery, R. G. Leber hereditary optic neuropathy in Australia. Aust. N. Z. J. Ophthalmol. 20, 177\u2013184 (1992).","journal-title":"Aust. N. Z. J. Ophthalmol."},{"key":"BFnrneurol2012167_CR119","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/S0002-9394(03)00099-0","volume":"136","author":"AA Sadun","year":"2003","unstructured":"Sadun, A. A.  et al. Extensive investigation of a large Brazilian pedigree of 11778\/haplogroup J Leber hereditary optic neuropathy. Am. J. Ophthalmol. 136, 231\u2013238 (2003).","journal-title":"Am. J. Ophthalmol."}],"container-title":["Nature Reviews Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/nrneurol.2012.167.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/nrneurol.2012.167","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/nrneurol.2012.167.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T06:27:59Z","timestamp":1650349679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nrneurol.2012.167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,4]]},"references-count":119,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["BFnrneurol2012167"],"URL":"https:\/\/doi.org\/10.1038\/nrneurol.2012.167","relation":{},"ISSN":["1759-4758","1759-4766"],"issn-type":[{"value":"1759-4758","type":"print"},{"value":"1759-4766","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,4]]},"assertion":[{"value":"4 September 2012","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"N. J. Newman has acted as a consultant for Santhera Pharmaceuticals.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}