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J. Esteve-Rudd, L. Fernández-Sánchez, P. Lax, J. Martín-Nieto, N. Cuenca; Effects of the Pesticide Rotenone on the Rat Retina: Degeneration of Photoreceptors, Impairments in Dopaminergic Neurons and Loss of Synaptic Connectivity. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2247.
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Rotenone is a pesticide that inhibits the mitochondrial respiratory chain complex I (NADH oxidase). The activity of this complex is usually reduced in the brain of Parkinson disease patients, and mutations in genes encoding some of its components are associated with Leber hereditary optic neuropathy. Patients suffering from these diseases exhibit retinal deficiencies, including altered electroretinograms (ERGs) and nerve fiber thinning. The aim of this work was to address the cellular and physiological impairments taking place in the retina of rotenone-treated rats.
Adult Sprague-Dawley rats were subcutaneously injected with rotenone (3 mg/kg) or vehicle every 48 h during 2 months. Thereafter, ERGs were recorded and rats sacrificed. Eyes were enucleated and retinas processed for protein extraction or immunohistochemistry. Proteins were subjected to immunoblotting analysis with tyrosine hydrolase (TH) antibodies. Retinal sections and whole-mounts were incubated with antibodies against specific neuronal markers, and visualized by immunofluorescence confocal microscopy.
A thinning of the outer nuclear and plexiform layers was observed, corresponding to a decrease of photoreceptor cell number and synaptic contacts between photoreceptors and bipolar or horizontal cells, respectively. As well, the ERGs of rotenone-treated rats exhibited significantly lowered amplitudes of a and b waves. We also found that levels of TH were decreased by ~70% in the retina, and that the dopaminergic cell number and plexus were greatly reduced, together with their synaptic contacts with AII amacrine cells.
Our results indicate that rotenone strongly damages photoreceptors and synaptic contacts with their postsynaptic neurons, as well as the retinal dopaminergic system, eliciting retinal neurodegeneration. Thus, rotenone treatment provides a suitable model of retinal degeneration induced by mitochondrial impairment-derived oxidative stress.
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