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

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.

• Authors: Julián Esteve-Rudd, Laura Fernández-Sánchez, Pedro Lax, Emilio De Juan, José Martín-Nieto, Nicolás Cuenca
• Journal: Neurobiology of disease (Neurobiol Dis) Vol. 44 Issue 1 Pg. 102-15 (Oct 2011) ISSN: 1095-953X [Electronic] United States
• PMID: 21742033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Uncoupling Agents
• Rotenone

Topics

• Amacrine Cells (drug effects)
• Animals
• Blotting, Western
• Body Weight (drug effects)
• Dopaminergic Neurons (drug effects)
• Electroretinography
• Immunohistochemistry
• Mitochondria (drug effects)
• Nerve Degeneration (chemically induced)
• Neurotoxicity Syndromes (pathology, psychology)
• Photoreceptor Cells (drug effects)
• Rats
• Rats, Sprague-Dawley
• Retina (cytology, drug effects, physiology)
• Retinal Ganglion Cells (drug effects)
• Reverse Transcriptase Polymerase Chain Reaction
• Rotenone (pharmacology)
• Synapses (drug effects)
• Uncoupling Agents (pharmacology)