A randomized, placebo-controlled trial of the benzoquinone idebenone in a mouse model of OPA1-related dominant optic atrophy reveals a limited therapeutic effect on retinal ganglion cell dendropathy and visual function

• Published in: Neuroscience Vol. 319; pp. 92 - 106
• Main Authors: Smith, T.G, Seto, S, Ganne, P, Votruba, M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 05.04.2016
• Subjects: Animals; Antioxidants - pharmacology; Blotting, Western; Dendrites - pathology; Disease Models, Animal; dominant optic atrophy; Female; GTP Phosphohydrolases - genetics; idebenone; Immunohistochemistry; Male; Mice; Mice, Mutant Strains; mitochondria; Neurology; NQO1; OPA1; Optic Atrophy, Autosomal Dominant - pathology; Random Allocation; retinal ganglion cell; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - pathology; Ubiquinone - analogs & derivatives; Ubiquinone - pharmacology; Visual Acuity - drug effects; NQO1; ganglion cell layer; DiI; INL; mitochondria; inner nuclear layer; IS; TBARS; ONL; outer nuclear layer; OPA1; thiobarbituric acid reactive species; NAD(P)H:quinone oxidoreductase-1; dominant optic atrophy; inner segment of photoreceptive layer; retinal ganglion cell; 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate; GLC; idebenone
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2016.01.042

Highlights • We conducted a trial of idebenone in an Opa1 mouse model of dominant optic atrophy. • We report the expression profile of NQO1 in the brain, retina and liver. • Mutant mice receiving treatment showed an early improvement in visual acuity. • In aged mice, vision and retinal dendritic loss were not prevented by idebenone. • Idebenone had a deleterious effect on wildtype retinal ganglion cells.