Neurodegeneration produced by rotenone in the mouse retina: a potential model to investigate environmental pesticide contributions to neurodegenerative diseases.
Rotenone is a widely used pesticide and fish toxin that inhibits complex I of the mitochondrial respiratory chain. Complex I dysfunction is linked to the degeneration of retinal ganglion cells in Leber's optic neuropathy. To study the association between environmental mitochondrial toxin exposure and neurodegeneration, mice were intravitreally microinjected with rotenone in one eye and with the vehicle dimethyl sulfoxide in the contralateral eye, as a within-subject control. The retinal ganglion cell layer (GCL) of eyes injected with rotenone became significantly thinner than that of the control eyes after 24 h, but not as early as 0.5 h. This reduction was observed using complex I histochemistry and with Nissl staining of cell bodies. After 24 h, retinal nerve fiber layer thickness was reduced by 89% and the number of GCL cells was reduced by 21% in rotenone-treated eyes. Cellular morphometric data (soma area, perimeter, and diameter) did not show overall differences, but there was a preferential reduction in the proportion of larger cells. Therefore, the reduction in GCL thickness 24 h after rotenone microinjection could be accounted for by cell loss and nerve fiber shrinkage, but not by overall soma size change. Rotenone-induced degeneration of the ganglion cell layer may be used as a convenient way to (1) evaluate mechanisms and treatments for the neurodegeneration produced by mitochondrial dysfunction and (2) investigate environmental pesticide contributions to neurodegenerative diseases.
Zhang
Xian
X
Institute for Neuroscience and Center for Molecular and Cellular Toxicology, University of Texas at Austin, Austin, Texas 78712, USA.
Jones
Dirk
D
Gonzalez-Lima
F
F
D000818:Animals; D004785:Environmental Pollutants / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D012162:Retinal Degeneration / Q000139:chemically induced* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D012402:Rotenone / Q000633:toxicity*; D013997:Time Factors
D004785:Environmental Pollutants; D007306:Insecticides; D012402:Rotenone