Ethambutol-induced optic neuropathy linked to OPA1 mutation and mitochondrial toxicity

详细信息    查看全文

• 作者：Virginie Guillet ; Arnaud Chevrollier ; Julien Cassereau ; Franck Letournel ; Naï ; g Gueguen ; Laurence Richard ; Valé ; rie Desquiret ; Christophe Verny ; Vincent Procaccio ; Patrizia Amati-Bonneau ; Pasc
• 关键词：Ethambutol ; OPA1 ; Autosomal dominant optic atrophy ; Mitochondria
• 刊名：Mitochondrion
• 出版年：2010
• 出版时间：March 2010
• 年：2010
• 卷：10
• 期：2
• 页码：115-124
• 全文大小：893 K

文摘

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.