title: Ethambutol-induced optic neuropathy linked to OPA1 mutation and mitochondrial toxicity.
abstract: Ethambutol (EMB), widely used in the treatment of tuberculosis, has been reported to cause Leber's hereditary optic neuropathy in patients carrying mitochondrial DNA mutations. We study the effect of EMB on mitochondrial metabolism in fibroblasts from controls and from a man carrying an OPA1 mutation, in whom the drug induced the development of autosomal dominant optic atrophy (ADOA). EMB produced a mitochondrial coupling defect together with a 25% reduction in complex IV activity. EMB induced the formation of vacuoles associated with decreased mitochondrial membrane potential and increased fragmentation of the mitochondrial network. Mitochondrial genetic variations may therefore be predisposing factors in EMB-induced ocular injury.
authors.affiliation: INSERM, U694, Angers, F-49000, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Guillet
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chevrollier
authors.forename: Julien
authors.initials: J
authors.lastname: Cassereau
authors.forename: Franck
authors.initials: F
authors.lastname: Letournel
authors.forename: Naïg
authors.initials: N
authors.lastname: Gueguen
authors.forename: Laurence
authors.initials: L
authors.lastname: Richard
authors.forename: Valérie
authors.initials: V
authors.lastname: Desquiret
authors.forename: Christophe
authors.initials: C
authors.lastname: Verny
authors.forename: Vincent
authors.initials: V
authors.lastname: Procaccio
authors.forename: Patrizia
authors.initials: P
authors.lastname: Amati-Bonneau
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
mesh_terms: D000995:Antitubercular Agents / Q000633:toxicity*; D002478:Cells, Cultured; D003576:Electron Transport Complex IV / Q000378:metabolism; D004977:Ethambutol / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D028361:Mitochondrial Diseases / Q000139:chemically induced*; D009154:Mutation; D009901:Optic Nerve Diseases / Q000139:chemically induced*
chemical_list: D000995:Antitubercular Agents; D004977:Ethambutol; D003576:Electron Transport Complex IV; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human