Neuroprotective effects of near-infrared light in an in vivo model of mitochondrial optic neuropathy.
Near-infrared light (NIL) promotes a wide range of biological effects including enhancement of energy production, gene expression and prevention of cell death. This is the first report of the in vivo neuroprotective effects of NIL against optic neuropathy induced by mitochondrial complex I inhibition. Subjects were pigmented rats that received single bilateral intravitreal doses of rotenone, a mitochondrial complex I inhibitor, or rotenone plus one of three different doses of NIL. Treatment effects were evaluated at behavioral, structural and neurochemical levels. Rotenone induced a decrease in visual function, as determined by changes in the dark-adapted illuminance sensitivity threshold, escape latency and rate of successful trials in a two-choice visual task, compared with vehicle-treated controls. Behavioral impairment correlated with a decrease in retinal and visual pathway metabolic activity, retinal nerve fiber layer thickness and ganglion cell layer cell density. These changes were prevented by NIL treatments in a dose-dependent manner. Whole-brain cytochrome oxidase and superoxide dismutase activities were also increased in NIL-treated subjects in a dose-dependent manner, suggesting an in vivo transcranial effect of NIL. In whole-brain membrane isolates, NIL prevented the rotenone-induced decrease in cell respiration. The results show that NIL treatment can effectively prevent the neurotoxic effects of rotenone and that it might be used in the treatment of neurodegenerative disorders associated with mitochondrial dysfunction.
Rojas
Julio C
JC
Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712, USA.
Lee
Jung
J
John
Joseph M
JM
Gonzalez-Lima
F
F
D000818:Animals; D001921:Brain / Q000528:radiation effects*; D042967:Electron Transport Complex I / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000528:radiation effects; D007150:Immunohistochemistry; D007259:Infrared Rays / Q000627:therapeutic use*; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D009901:Optic Nerve Diseases / Q000503:physiopathology* / Q000532:radiotherapy*; D051381:Rats; D020318:Rats, Long-Evans; D012402:Rotenone / Q000633:toxicity; D013482:Superoxide Dismutase / Q000528:radiation effects; D014475:Uncoupling Agents / Q000633:toxicity
D014475:Uncoupling Agents; D012402:Rotenone; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I