Cargando…

Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy

Background: Ethambutol-induced optic neuropathy (EON) is a well-recognized ocular complication in patients who take ethambutol as a tuberculosis treatment. The aim of the current study was to investigate the presence of mitochondrial mutations, including OPA1 and Leber’s hereditary optic neuropathy...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Xiao-Hui, Xie, Yue, Xu, Quan-Gang, Cao, Kai, Xu, Ke, Jin, Zi-Bing, Li, Yang, Wei, Shi-Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525703/
https://www.ncbi.nlm.nih.gov/pubmed/34676220
http://dx.doi.org/10.3389/fcell.2021.754676
_version_ 1784585737752018944
author Zhang, Xiao-Hui
Xie, Yue
Xu, Quan-Gang
Cao, Kai
Xu, Ke
Jin, Zi-Bing
Li, Yang
Wei, Shi-Hui
author_facet Zhang, Xiao-Hui
Xie, Yue
Xu, Quan-Gang
Cao, Kai
Xu, Ke
Jin, Zi-Bing
Li, Yang
Wei, Shi-Hui
author_sort Zhang, Xiao-Hui
collection PubMed
description Background: Ethambutol-induced optic neuropathy (EON) is a well-recognized ocular complication in patients who take ethambutol as a tuberculosis treatment. The aim of the current study was to investigate the presence of mitochondrial mutations, including OPA1 and Leber’s hereditary optic neuropathy (LHON)-mitochondrial DNA (mtDNA), in patients with EON and to determine their effect on clinical features of these patients. Methods: All 47 patients underwent clinical evaluations, including best-corrected visual acuity, fundus examination, and color fundus photography; 37 patients were then followed up over time. Molecular screening methods, including PCR-based sequencing of the OPA1 gene and LHON-mtDNA mutations, together with targeted exome sequencing, were used to detect mutations. Results: We detected 15 OPA1 mutations in 18 patients and two LHON-mtDNA mutations in four patients, for an overall mutation detection rate of 46.8%. The mean presentation age was significantly younger in the patients with the mitochondrial mutations (27.5 years) than in those without mutations (48 years). Fundus examination revealed a greater prevalence of optic disc hyperemia in the patients with mutations (70.5%) than without mutations (48%). Half of the patients with mutations and 91% of the patients without mutations had improved vision. After adjusting for confounders, the logistic regression revealed that the patients with optic disc pallor on the first visit (p = 0.004) or the patients with the mitochondrial mutations (p < 0.001) had a poorer vision prognosis. Conclusion: Our results indicated that carriers with OPA1 mutations might be more vulnerable for the toxicity of EMB to develop EON.
format Online
Article
Text
id pubmed-8525703
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-85257032021-10-20 Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy Zhang, Xiao-Hui Xie, Yue Xu, Quan-Gang Cao, Kai Xu, Ke Jin, Zi-Bing Li, Yang Wei, Shi-Hui Front Cell Dev Biol Cell and Developmental Biology Background: Ethambutol-induced optic neuropathy (EON) is a well-recognized ocular complication in patients who take ethambutol as a tuberculosis treatment. The aim of the current study was to investigate the presence of mitochondrial mutations, including OPA1 and Leber’s hereditary optic neuropathy (LHON)-mitochondrial DNA (mtDNA), in patients with EON and to determine their effect on clinical features of these patients. Methods: All 47 patients underwent clinical evaluations, including best-corrected visual acuity, fundus examination, and color fundus photography; 37 patients were then followed up over time. Molecular screening methods, including PCR-based sequencing of the OPA1 gene and LHON-mtDNA mutations, together with targeted exome sequencing, were used to detect mutations. Results: We detected 15 OPA1 mutations in 18 patients and two LHON-mtDNA mutations in four patients, for an overall mutation detection rate of 46.8%. The mean presentation age was significantly younger in the patients with the mitochondrial mutations (27.5 years) than in those without mutations (48 years). Fundus examination revealed a greater prevalence of optic disc hyperemia in the patients with mutations (70.5%) than without mutations (48%). Half of the patients with mutations and 91% of the patients without mutations had improved vision. After adjusting for confounders, the logistic regression revealed that the patients with optic disc pallor on the first visit (p = 0.004) or the patients with the mitochondrial mutations (p < 0.001) had a poorer vision prognosis. Conclusion: Our results indicated that carriers with OPA1 mutations might be more vulnerable for the toxicity of EMB to develop EON. Frontiers Media S.A. 2021-10-05 /pmc/articles/PMC8525703/ /pubmed/34676220 http://dx.doi.org/10.3389/fcell.2021.754676 Text en Copyright © 2021 Zhang, Xie, Xu, Cao, Xu, Jin, Li and Wei. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zhang, Xiao-Hui
Xie, Yue
Xu, Quan-Gang
Cao, Kai
Xu, Ke
Jin, Zi-Bing
Li, Yang
Wei, Shi-Hui
Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy
title Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy
title_full Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy
title_fullStr Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy
title_full_unstemmed Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy
title_short Mitochondrial Mutations in Ethambutol-Induced Optic Neuropathy
title_sort mitochondrial mutations in ethambutol-induced optic neuropathy
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525703/
https://www.ncbi.nlm.nih.gov/pubmed/34676220
http://dx.doi.org/10.3389/fcell.2021.754676
work_keys_str_mv AT zhangxiaohui mitochondrialmutationsinethambutolinducedopticneuropathy
AT xieyue mitochondrialmutationsinethambutolinducedopticneuropathy
AT xuquangang mitochondrialmutationsinethambutolinducedopticneuropathy
AT caokai mitochondrialmutationsinethambutolinducedopticneuropathy
AT xuke mitochondrialmutationsinethambutolinducedopticneuropathy
AT jinzibing mitochondrialmutationsinethambutolinducedopticneuropathy
AT liyang mitochondrialmutationsinethambutolinducedopticneuropathy
AT weishihui mitochondrialmutationsinethambutolinducedopticneuropathy