Research progress of risk factors of Leber’s hereditary optic neuropathy_Chinese Journal of Ocular Fundus Diseases

Authors：

Gao Yinglong ^1,2,3 ,  Yu Jialing ⁴

1. Department of Pediatric Surgery, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China;
2. National Clinical Research Center For Child Health, Hangzhou 310052, China;
3. National Regional Medical Center for Children, Hangzhou 310052, China;
4. Department of Reproductive Genetics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, China;

Corresponding author：

Yu Jialing, Email: jialingyu@zju.edu.cn

Keywords：

Leber’s hereditary optic neuropathy; Mitochondria; Secondary mitochondrial mutation; Mitochondrial haploid type; Nuclear modifier gene; Environmental factors; Review

DOI：

10.3760/cma.j.cn511434-20220829-00480

Video：

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Abstract Full text Figures/Tables Video References Cited by

Leber’s hereditary optic neuropathy (LHON) is a paradigm maternal hereditary eye disease, mainly involving the retinal and macular fibers of the optic disc in the anterior ethmoid plate of the sclera. LHON has the characteristics of sex bias among males and incomplete penetrance. Primary mitochondrial DNA mutations m.11778G>A, m. 14484T>C, m.3460G>A are the molecular basis of LHON. However, other risk factors, such as secondary mitochondrial DNA mutations, mitochondrial haplotypes, nuclear modification genes, estrogen, vitamin B12 and environmental factors, work together to affect its phenotypic expression. The clinical diagnosis of LHON mainly limited to the detection of the primary mutation site of mitochondrial DNA. Therefore, comprehensive analysis of multiple risk factors of LHON will facilitate to construct multi-dimensional model of prevention, diagnosis and treatment system, which provide accurate and individualized medical services for patients. These may alleviate the incidence in LHON families. It also provides new ideas and different angles for the in-depth study of the pathogenesis of LHON.

Citation： Gao Yinglong, Yu Jialing. Research progress of risk factors of Leber’s hereditary optic neuropathy. Chinese Journal of Ocular Fundus Diseases, 2023, 39(7): 600-604. doi: 10.3760/cma.j.cn511434-20220829-00480 Copy

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2.	Carelli V, La Morgia C, Valentino ML, et alRetinal ganglion cell neurodegeneration in mitochondrial inherited disorders[J]. Biochim Biophys Acta200917875518528. DOI: 10.1016/j.bbabio.2009.02.024.
3.	Jia Z, Wang X, Qin Y, et alCoronary heart disease is associated with a mutation in mitochondrial tRNA[J]. Hum Mol Genet2013222040644073. DOI: 10.1093/hmg/ddt256.
4.	Xu C, Tong L, Rao J, et al. Heteroplasmic and homoplasmic m. 616T>C in mitochondria tRNAPhe promote isolated chronic kidney disease and hyperuricemia[J]. JCI Insight, 2022, 7(11): e157418[2022-06-08]. https://europepmc.org/article/MED/35472031. DOI: 10.1172/jci.insight.157418.
5.	Jiang P, Wang M, Xue L, et alA Hypertension-associated tRNA^Ala mutation alters tRNA metabolism and mitochondrial function[J]. Mol Cell Biol2016361419201930. DOI: 10.1128/mcb.00199-16.
6.	Ji Y, Zhang J, Lu Y, et alComplex I mutations synergize to worsen the phenotypic expression of Leber's hereditary optic neuropathy[J]. J Biol Chem2020295381322413238. DOI: 10.1074/jbc.RA120.014603.
7.	Zhang J, Ji Y, Liu X, et alLeber's hereditary optic neuropathy caused by a mutation in mitochondrial tRNA(Thr) in eight Chinese pedigrees[J]. Mitochondrion2018428491. DOI: 10.1016/j.mito.2017.12.003.
8.	Ji Y, Zhang J, Liang M, et alMitochondrial tRNA variants in 811 Chinese probands with Leber's hereditary optic neuropathy[J]. Mitochondrion2022655666. DOI: 10.1016/j.mito.2022.05.003.
9.	Shu L, Zhang YM, Huang XX, et alComplete mitochondrial DNA sequence analysis in two southern Chinese pedigrees with Leber hereditary optic neuropathy revealed secondary mutations along with the primary mutation[J]. Int J Ophthalmol2012512831. DOI: 10.3980/j.issn.2222-3959.2012.01.06.
10.	Vandeputte J, Van Heetvelde M, Van Cauwenbergh C, et alMild Leber hereditary optic neuropathy (LHON) in a Western European family due to the rare Asian m. 14502T>C variant in the MT-ND6 gene[J]. Ophthalmic Genet2021424440445. DOI: 10.1080/13816810.2021.1913611.
11.	Ji Y, Liang M, Zhang J, et alMitochondrial ND1 variants in 1281 Chinese subjects with Leber's hereditary optic neuropathy[J]. Invest Ophthalmol Vis Sci201657623772389. DOI: 10.1167/iovs.16-19243.
12.	Zhang J, Ji Y, Lu Y, et alLeber's hereditary optic neuropathy (LHON)-associated ND5 12338T > C mutation altered the assembly and function of complex I, apoptosis and mitophagy[J]. Hum Mol Genet2018271119992011. DOI: 10.1093/hmg/ddy107.
13.	Ji Y, Zhang J, Yu J, et alContribution of mitochondrial ND1 3394T>C mutation to the phenotypic manifestation of Leber's hereditary optic neuropathy[J]. Hum Mol Genet201928915151529. DOI: 10.1093/hmg/ddy450.
14.	Hudson G, Carelli V, Spruijt L, et alClinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background[J]. Am J Hum Genet2007812228233. DOI: 10.1086/519394.
15.	Torroni A, Petrozzi M, D'urbano L, et alHaplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484[J]. Am J Hum Genet199760511071121.
16.	Brown MD, Sun F, Wallace DCClustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage[J]. Am J Hum Genet1997602381387.
17.	Ji Y, Zhang AM, Jia X, et al. Mitochondrial DNA haplogroups M7b1'2 and M8a affect clinical expression of leber hereditary optic neuropathy in Chinese families with the m. 11778G-->a mutation[J]. Am J Hum Genet2008836760768. DOI: 10.1016/j.ajhg.2008.11.002.
18.	Zhang AM, Jia X, Bi R, et al. Mitochondrial DNA haplogroup background affects LHON, but not suspected LHON, in Chinese patients[J/OL]. PLoS One, 2011, 6(11): e27750[2011-11-15]. https://europepmc.org/article/MED/22110754. DOI: 10.1371/journal.pone.0027750.
19.	Zhang J, Zhao F, Fu Q, et alMitochondrial haplotypes may modulate the phenotypic manifestation of the LHON-associated m. 14484T>C (MT-ND6) mutation in Chinese families[J]. Mitochondrion2013136772781. DOI: 10.1016/j.mito.2013.05.002.
20.	Hinttala R, Kervinen M, Uusimaa J, et alAnalysis of functional consequences of haplogroup J polymorphisms m. 4216T>C and m. 3866T>C in human MT-ND1: mutagenesis of homologous positions in Escherichia coli[J]. Mitochondrion2010104358361. DOI: 10.1016/j.mito.2010.02.002.
21.	Bi R, Zhang AM, Jia X, et alComplete mitochondrial DNA genome sequence variation of Chinese families with mutation m. 3635G>A and Leber hereditary optic neuropathy[J]. Mol Vis20121830873094.
22.	Dai Y, Wang C, Nie Z, et alMutation analysis of Leber's hereditary optic neuropathy using a multi-gene panel[J]. Biomed Rep2018815158. DOI: 10.3892/br.2017.1014.
23.	Bu X, Rotter JILeber hereditary optic neuropathy: estimation of number of embryonic precursor cells and disease threshold in heterozygous affected females at the X-linked locus[J]. Clin Genet1992423143148. DOI: 10.1111/j.1399-0004.1992.tb03226.x.
24.	Phasukkijwatana N, Kunhapan B, Stankovich J, et alGenome-wide linkage scan and association study of PARL to the expression of LHON families in Thailand[J]. Hum Genet201012813949. DOI: 10.1007/s00439-010-0821-8.
25.	Jiang P, Jin X, Peng Y, et alThe exome sequencing identified the mutation in YARS2 encoding the mitochondrial tyrosyl-tRNA synthetase as a nuclear modifier for the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation[J]. Hum Mol Genet2016253584596. DOI: 10.1093/hmg/ddv498.
26.	Jin X, Zhang J, Yi Q, et alLeber's hereditary optic neuropathy arising from the synergy between ND1 3635G>A mutation and mitochondrial YARS2 Mutations[J]. Invest Ophthalmol Vis Sci202162722. DOI: 10.1001/jamaneurol.2016.4357.
27.	Jin X, Zhang Z, Nie Z, et alAn animal model for mitochondrial tyrosyl-tRNA synthetase deficiency reveals links between oxidative phosphorylation and retinal function[J]. J Biol Chem2021296100437. DOI: 10.1016/j.jbc.2021.100437.
28.	Devenport DThe cell biology of planar cell polarity[J]. J Biol Chem20142072171179. DOI: 10.1083/jcb.201408039.
29.	Crompton LA, Du Roure C, Rodriguez TAEarly embryonic expression patterns of the mouse Flamingo and Prickle orthologues[J]. Dev Dyn20072361131373143. DOI: 10.1002/dvdy.21338.
30.	Yu J, Liang X, Ji Y, et alPRICKLE3 linked to ATPase biogenesis manifested Leber's hereditary optic neuropathy[J]. J Clin Invest2020130949354946. DOI: 10.1172/JCI134965.
31.	Nie Z, Wang C, Chen J, et alAbnormal morphology and function in retinal ganglion cells derived from patients-specific iPSCs generated from individuals with Leber's hereditary optic neuropathy[J]. Hum Mol Genet2022322231243. DOI: 10.1093/hmg/ddac190.
32.	Giordano C, Montopoli M, Perli E, et al. Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy[J]. Brain, 2011, 134(Pt 1): 220-234. DOI: 10.1093/brain/awq276.
33.	Pisano A, Preziuso C, Iommarini L, et alTargeting estrogen receptor β as preventive therapeutic strategy for Leber's hereditary optic neuropathy[J]. Hum Mol Genet2015242469216931. DOI: 10.1093/hmg/ddv396.
34.	Hannibal L, Lysne V, Bjørke-Monsen AL, et alBiomarkers and algorithms for the diagnosis of vitamin B12 deficiency[J]. Front Mol Biosci2016327. DOI: 10.3389/fmolb.2016.00027.
35.	Allen LH, Miller JW, De Groot L, et alBiomarkers of nutrition for development (BOND): vitamin B-12 review[J]. J Nutr2018148Suppl 4S19952027. DOI: 10.1093/jn/nxy201.
36.	Sadun AAMetabolic optic neuropathies[J]. Semin Ophthalmol20021712932. DOI: 10.1076/soph.17.1.29.10290.
37.	Zibold J, Von Livonius B, Kolarova H, et alVitamin B12 in Leber hereditary optic neuropathy mutation carriers: a prospective cohort study[J]. Orphanet J Rare Dis2022171310. DOI: 10.1186/s13023-022-02453-z.
38.	Kirkman MA, Yu-Wai-Man P, Korsten A, et al. Gene-environment interactions in Leber hereditary optic neuropathy[J]. Brain, 2009, 132(Pt 9): 2317-2326. DOI: 10.1093/brain/awp158.
39.	Giordano C, Iommarini L, Giordano L, et al. Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy[J]. Brain, 2014, 137(Pt 2): 335-353. DOI: 10.1093/brain/awt343.
40.	Giordano L, Deceglie S, D'adamo P, et alCigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways[J]. Cell Death Dis2015612e2021. DOI: 10.1038/cddis.2015.364.
41.	Zaslavsky K, Margolin EALeber's hereditary optic neuropathy in older individuals because of increased alcohol consumption during the COVID-19 pandemic[J]. J Neuroophthalmol2021413316320. DOI: 10.1097/wno.0000000000001333.
42.	Yu-Wai-Man P, Griffiths PG, Chinnery PFMitochondrial optic neuropathies - disease mechanisms and therapeutic strategies[J]. Prog Retin Eye Res201130281114. DOI: 10.1016/j.preteyeres.2010.11.002.
43.	López-Gallardo E, Emperador S, Hernández-Ainsa C, et alFood derived respiratory complex I inhibitors modify the effect of Leber hereditary optic neuropathy mutations[J]. Food Chem Toxicol20181208997. DOI: 10.1016/j.fct.2018.07.014.
44.	Kogachi K, Ter-Zakarian A, Asanad S, et alToxic medications in Leber's hereditary optic neuropathy[J]. Mitochondrion201946270277. DOI: 10.1016/j.mito.2018.07.007.
45.	Reinert MC, Pacheu-Grau D, Catarino CB, et alSulthiame impairs mitochondrial function in vitro and may trigger onset of visual loss in Leber hereditary optic neuropathy[J]. Orphanet J Rare Dis202116164. DOI: 10.1186/s13023-021-01690-y.

1. Carelli V, La Morgia C, Yu-Wai-Man PMitochondrial optic neuropathies[J]. Handb Clin Neurol20231942342. DOI: 10.1016/b978-0-12-821751-1.00010-5.
2. Carelli V, La Morgia C, Valentino ML, et alRetinal ganglion cell neurodegeneration in mitochondrial inherited disorders[J]. Biochim Biophys Acta200917875518528. DOI: 10.1016/j.bbabio.2009.02.024.
3. Jia Z, Wang X, Qin Y, et alCoronary heart disease is associated with a mutation in mitochondrial tRNA[J]. Hum Mol Genet2013222040644073. DOI: 10.1093/hmg/ddt256.
4. Xu C, Tong L, Rao J, et al. Heteroplasmic and homoplasmic m. 616T>C in mitochondria tRNAPhe promote isolated chronic kidney disease and hyperuricemia[J]. JCI Insight, 2022, 7(11): e157418[2022-06-08]. https://europepmc.org/article/MED/35472031. DOI: 10.1172/jci.insight.157418.
5. Jiang P, Wang M, Xue L, et alA Hypertension-associated tRNA^Ala mutation alters tRNA metabolism and mitochondrial function[J]. Mol Cell Biol2016361419201930. DOI: 10.1128/mcb.00199-16.
6. Ji Y, Zhang J, Lu Y, et alComplex I mutations synergize to worsen the phenotypic expression of Leber's hereditary optic neuropathy[J]. J Biol Chem2020295381322413238. DOI: 10.1074/jbc.RA120.014603.
7. Zhang J, Ji Y, Liu X, et alLeber's hereditary optic neuropathy caused by a mutation in mitochondrial tRNA(Thr) in eight Chinese pedigrees[J]. Mitochondrion2018428491. DOI: 10.1016/j.mito.2017.12.003.
8. Ji Y, Zhang J, Liang M, et alMitochondrial tRNA variants in 811 Chinese probands with Leber's hereditary optic neuropathy[J]. Mitochondrion2022655666. DOI: 10.1016/j.mito.2022.05.003.
9. Shu L, Zhang YM, Huang XX, et alComplete mitochondrial DNA sequence analysis in two southern Chinese pedigrees with Leber hereditary optic neuropathy revealed secondary mutations along with the primary mutation[J]. Int J Ophthalmol2012512831. DOI: 10.3980/j.issn.2222-3959.2012.01.06.
10. Vandeputte J, Van Heetvelde M, Van Cauwenbergh C, et alMild Leber hereditary optic neuropathy (LHON) in a Western European family due to the rare Asian m. 14502T>C variant in the MT-ND6 gene[J]. Ophthalmic Genet2021424440445. DOI: 10.1080/13816810.2021.1913611.
11. Ji Y, Liang M, Zhang J, et alMitochondrial ND1 variants in 1281 Chinese subjects with Leber's hereditary optic neuropathy[J]. Invest Ophthalmol Vis Sci201657623772389. DOI: 10.1167/iovs.16-19243.
12. Zhang J, Ji Y, Lu Y, et alLeber's hereditary optic neuropathy (LHON)-associated ND5 12338T > C mutation altered the assembly and function of complex I, apoptosis and mitophagy[J]. Hum Mol Genet2018271119992011. DOI: 10.1093/hmg/ddy107.
13. Ji Y, Zhang J, Yu J, et alContribution of mitochondrial ND1 3394T>C mutation to the phenotypic manifestation of Leber's hereditary optic neuropathy[J]. Hum Mol Genet201928915151529. DOI: 10.1093/hmg/ddy450.
14. Hudson G, Carelli V, Spruijt L, et alClinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background[J]. Am J Hum Genet2007812228233. DOI: 10.1086/519394.
15. Torroni A, Petrozzi M, D'urbano L, et alHaplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484[J]. Am J Hum Genet199760511071121.
16. Brown MD, Sun F, Wallace DCClustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage[J]. Am J Hum Genet1997602381387.
17. Ji Y, Zhang AM, Jia X, et al. Mitochondrial DNA haplogroups M7b1'2 and M8a affect clinical expression of leber hereditary optic neuropathy in Chinese families with the m. 11778G-->a mutation[J]. Am J Hum Genet2008836760768. DOI: 10.1016/j.ajhg.2008.11.002.
18. Zhang AM, Jia X, Bi R, et al. Mitochondrial DNA haplogroup background affects LHON, but not suspected LHON, in Chinese patients[J/OL]. PLoS One, 2011, 6(11): e27750[2011-11-15]. https://europepmc.org/article/MED/22110754. DOI: 10.1371/journal.pone.0027750.
19. Zhang J, Zhao F, Fu Q, et alMitochondrial haplotypes may modulate the phenotypic manifestation of the LHON-associated m. 14484T>C (MT-ND6) mutation in Chinese families[J]. Mitochondrion2013136772781. DOI: 10.1016/j.mito.2013.05.002.
20. Hinttala R, Kervinen M, Uusimaa J, et alAnalysis of functional consequences of haplogroup J polymorphisms m. 4216T>C and m. 3866T>C in human MT-ND1: mutagenesis of homologous positions in Escherichia coli[J]. Mitochondrion2010104358361. DOI: 10.1016/j.mito.2010.02.002.
21. Bi R, Zhang AM, Jia X, et alComplete mitochondrial DNA genome sequence variation of Chinese families with mutation m. 3635G>A and Leber hereditary optic neuropathy[J]. Mol Vis20121830873094.
22. Dai Y, Wang C, Nie Z, et alMutation analysis of Leber's hereditary optic neuropathy using a multi-gene panel[J]. Biomed Rep2018815158. DOI: 10.3892/br.2017.1014.
23. Bu X, Rotter JILeber hereditary optic neuropathy: estimation of number of embryonic precursor cells and disease threshold in heterozygous affected females at the X-linked locus[J]. Clin Genet1992423143148. DOI: 10.1111/j.1399-0004.1992.tb03226.x.
24. Phasukkijwatana N, Kunhapan B, Stankovich J, et alGenome-wide linkage scan and association study of PARL to the expression of LHON families in Thailand[J]. Hum Genet201012813949. DOI: 10.1007/s00439-010-0821-8.
25. Jiang P, Jin X, Peng Y, et alThe exome sequencing identified the mutation in YARS2 encoding the mitochondrial tyrosyl-tRNA synthetase as a nuclear modifier for the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation[J]. Hum Mol Genet2016253584596. DOI: 10.1093/hmg/ddv498.
26. Jin X, Zhang J, Yi Q, et alLeber's hereditary optic neuropathy arising from the synergy between ND1 3635G>A mutation and mitochondrial YARS2 Mutations[J]. Invest Ophthalmol Vis Sci202162722. DOI: 10.1001/jamaneurol.2016.4357.
27. Jin X, Zhang Z, Nie Z, et alAn animal model for mitochondrial tyrosyl-tRNA synthetase deficiency reveals links between oxidative phosphorylation and retinal function[J]. J Biol Chem2021296100437. DOI: 10.1016/j.jbc.2021.100437.
28. Devenport DThe cell biology of planar cell polarity[J]. J Biol Chem20142072171179. DOI: 10.1083/jcb.201408039.
29. Crompton LA, Du Roure C, Rodriguez TAEarly embryonic expression patterns of the mouse Flamingo and Prickle orthologues[J]. Dev Dyn20072361131373143. DOI: 10.1002/dvdy.21338.
30. Yu J, Liang X, Ji Y, et alPRICKLE3 linked to ATPase biogenesis manifested Leber's hereditary optic neuropathy[J]. J Clin Invest2020130949354946. DOI: 10.1172/JCI134965.
31. Nie Z, Wang C, Chen J, et alAbnormal morphology and function in retinal ganglion cells derived from patients-specific iPSCs generated from individuals with Leber's hereditary optic neuropathy[J]. Hum Mol Genet2022322231243. DOI: 10.1093/hmg/ddac190.
32. Giordano C, Montopoli M, Perli E, et al. Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy[J]. Brain, 2011, 134(Pt 1): 220-234. DOI: 10.1093/brain/awq276.
33. Pisano A, Preziuso C, Iommarini L, et alTargeting estrogen receptor β as preventive therapeutic strategy for Leber's hereditary optic neuropathy[J]. Hum Mol Genet2015242469216931. DOI: 10.1093/hmg/ddv396.
34. Hannibal L, Lysne V, Bjørke-Monsen AL, et alBiomarkers and algorithms for the diagnosis of vitamin B12 deficiency[J]. Front Mol Biosci2016327. DOI: 10.3389/fmolb.2016.00027.
35. Allen LH, Miller JW, De Groot L, et alBiomarkers of nutrition for development (BOND): vitamin B-12 review[J]. J Nutr2018148Suppl 4S19952027. DOI: 10.1093/jn/nxy201.
36. Sadun AAMetabolic optic neuropathies[J]. Semin Ophthalmol20021712932. DOI: 10.1076/soph.17.1.29.10290.
37. Zibold J, Von Livonius B, Kolarova H, et alVitamin B12 in Leber hereditary optic neuropathy mutation carriers: a prospective cohort study[J]. Orphanet J Rare Dis2022171310. DOI: 10.1186/s13023-022-02453-z.
38. Kirkman MA, Yu-Wai-Man P, Korsten A, et al. Gene-environment interactions in Leber hereditary optic neuropathy[J]. Brain, 2009, 132(Pt 9): 2317-2326. DOI: 10.1093/brain/awp158.
39. Giordano C, Iommarini L, Giordano L, et al. Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy[J]. Brain, 2014, 137(Pt 2): 335-353. DOI: 10.1093/brain/awt343.
40. Giordano L, Deceglie S, D'adamo P, et alCigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways[J]. Cell Death Dis2015612e2021. DOI: 10.1038/cddis.2015.364.
41. Zaslavsky K, Margolin EALeber's hereditary optic neuropathy in older individuals because of increased alcohol consumption during the COVID-19 pandemic[J]. J Neuroophthalmol2021413316320. DOI: 10.1097/wno.0000000000001333.
42. Yu-Wai-Man P, Griffiths PG, Chinnery PFMitochondrial optic neuropathies - disease mechanisms and therapeutic strategies[J]. Prog Retin Eye Res201130281114. DOI: 10.1016/j.preteyeres.2010.11.002.
43. López-Gallardo E, Emperador S, Hernández-Ainsa C, et alFood derived respiratory complex I inhibitors modify the effect of Leber hereditary optic neuropathy mutations[J]. Food Chem Toxicol20181208997. DOI: 10.1016/j.fct.2018.07.014.
44. Kogachi K, Ter-Zakarian A, Asanad S, et alToxic medications in Leber's hereditary optic neuropathy[J]. Mitochondrion201946270277. DOI: 10.1016/j.mito.2018.07.007.
45. Reinert MC, Pacheu-Grau D, Catarino CB, et alSulthiame impairs mitochondrial function in vitro and may trigger onset of visual loss in Leber hereditary optic neuropathy[J]. Orphanet J Rare Dis202116164. DOI: 10.1186/s13023-021-01690-y.

Chinese Journal of Ocular Fundus Diseases

Research progress of risk factors of Leber’s hereditary optic neuropathy

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