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Neurobiol Dis. 2011 Oct;44(1):102-15. doi: 10.1016/j.nbd.2011.06.009. Epub 2011 Jun 25.

Rotenone induces degeneration of photoreceptors and impairs the dopaminergic system in the rat retina.

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1
Departamento de Fisiología, Genética y Microbiología, Facultad de Ciencias, Universidad de Alicante, E-03080 Alicante, Spain. j.esteve@ua.es

Abstract

Rotenone is a widely used pesticide and a potent inhibitor of mitochondrial complex I (NADH-quinone reductase) that elicits the degeneration of dopaminergic neurons and thereby the appearance of a parkinsonian syndrome. Here we have addressed the alterations induced by rotenone at the functional, morphological and molecular levels in the retina, including those involving both dopaminergic and non-dopaminergic retinal neurons. Rotenone-treated rats showed abnormalities in equilibrium, postural instability and involuntary movements. In their outer retina we observed a loss of photoreceptors, and a reduced synaptic connectivity between those remaining and their postsynaptic neurons. A dramatic loss of mitochondria was observed in the inner segments, as well as in the axon terminals of photoreceptors. In the inner retina we observed a decrease in the expression of dopaminergic cell molecular markers, including loss of tyrosine hydroxylase immunoreactivity, associated with a reduction of the dopaminergic plexus and cell bodies. An increase in immunoreactivity of AII amacrine cells for parvalbumin, a Ca(2+)-scavenging protein, was also detected. These abnormalities were accompanied by a decrease in the amplitude of scotopic and photopic a- and b-waves and an increase in the b-wave implicit time, as well as by a lower amplitude and greater latency in oscillatory potentials. These results indicate that rotenone induces loss of vision by promoting photoreceptor cell death and impairment of the dopaminergic retinal system.

PMID:
21742033
DOI:
10.1016/j.nbd.2011.06.009
[Indexed for MEDLINE]

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