title: 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: Departamento de Fisiología, Genética y Microbiología, Facultad de Ciencias, Universidad de Alicante, E-03080 Alicante, Spain. j.esteve@ua.es
authors: Julián
authors: J
authors: Esteve-Rudd
authors: Laura
authors: L
authors: Fernández-Sánchez
authors: Pedro
authors: P
authors: Lax
authors: Emilio
authors: E
authors: De Juan
authors: José
authors: J
authors: Martín-Nieto
authors: Nicolás
authors: N
authors: Cuenca
mesh_terms: D025042:Amacrine Cells / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects*; D004596:Electroretinography; D007150:Immunohistochemistry; D008928:Mitochondria / Q000187:drug effects; D009410:Nerve Degeneration / Q000139:chemically induced*; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000523:psychology; D010786:Photoreceptor Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012402:Rotenone / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects; D014475:Uncoupling Agents / Q000494:pharmacology*
chemical_list: D014475:Uncoupling Agents; D012402:Rotenone