title: Mouse model of optic neuropathy caused by mitochondrial complex I dysfunction.
abstract: We developed a mouse model of optic neuropathy caused by mitochondrial complex I dysfunction by intravitreal administration of rotenone, a complex I inhibitor, in CBA/J mice. Retinal thickness was measured in sections stained histochemically for complex I enzymatic activity. The retinal ganglion cell layer of eyes injected with rotenone was significantly thinner than that of the control eyes injected with the vehicle dimethyl sulfoxide at 1, 24, and 48-h survival time groups. The largest reduction was 43% at 24-h post-injection. This effect is consistent with the degeneration of retinal ganglion cells in Leber's hereditary optic neuropathy. This is the first animal model of optic neuropathy caused by mitochondrial dysfunction, and it could be used as a quick and convenient way to test new treatments for mitochondrial neurodegenerative diseases.
authors.affiliation: Institute for Neuroscience and Center for Molecular and Cellular Toxicology, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Dirk
authors.initials: D
authors.lastname: Jones
authors.forename: F
authors.initials: F
authors.lastname: Gonzalez-Lima
mesh_terms: D000818:Animals; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008928:Mitochondria / Q000201:enzymology*; D028361:Mitochondrial Diseases / Q000139:chemically induced / Q000150:complications*; D009901:Optic Nerve Diseases / Q000209:etiology*; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D011808:Quinone Reductases / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D012402:Rotenone / Q000494:pharmacology; D013997:Time Factors; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D014677:Pharmaceutical Vehicles; D014475:Uncoupling Agents; D012402:Rotenone; C041831:NADH dehydrogenase (quinone); D011808:Quinone Reductases; D004121:Dimethyl Sulfoxide