Mouse model of optic neuropathy caused by mitochondrial complex I dysfunction

doi:10.1016/S0304-3940(02)00327-0

Neuroscience Letters

Volume 326, Issue 2, 28 June 2002, Pages 97-100

https://doi.org/10.1016/S0304-3940(02)00327-0 Get rights and content

Abstract

We developed a mouse model of optic neuropathy caused by mitochondrial complex I dysfunction by intravitreal administration of rotenone, a complex I inhibitor, in CBA/J mice. Retinal thickness was measured in sections stained histochemically for complex I enzymatic activity. The retinal ganglion cell layer of eyes injected with rotenone was significantly thinner than that of the control eyes injected with the vehicle dimethyl sulfoxide at 1, 24, and 48-h survival time groups. The largest reduction was 43% at 24-h post-injection. This effect is consistent with the degeneration of retinal ganglion cells in Leber's hereditary optic neuropathy. This is the first animal model of optic neuropathy caused by mitochondrial dysfunction, and it could be used as a quick and convenient way to test new treatments for mitochondrial neurodegenerative diseases.

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Acknowledgements

We thank Drs Juan Salinas and Yvon Delville for use of their equipment. Supported by NIEHS grant ES07784.

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Citation Excerpt :
To develop effective treatment strategies and to better understand the disease mechanisms, it is important that faithful animal models presenting similarity with the human disease are created. The majority of existing rodent models for LHON disease is created based on either direct injection of complex I inhibitor into the eye or genetic manipulation of complex I subunits [9–13]. Rotenone is a potent inhibitor of the mitochondrial complex I [14].
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Mouse model of optic neuropathy caused by mitochondrial complex I dysfunction

Abstract

Section snippets

Acknowledgements

J. Neurol. Sci.

J. Biol. Chem.

Vis. Res.

Am. J. Hum. Genet.

Biochim. Biophys. Acta

J. Mol. Biol.

Effects of chronic sodium azide on brain and muscle cytochrome oxidase activity: a potential model to investigate environmental contributions to neurodegenerative diseases

J. Toxicol. Environ. Health. Part A

Leber's hereditary optic neuropathy: clinical and molecular genetic findings in a patient with a new mutation in the ND6 gene

Graefes Arch. Clin. Exp. Ophthalmol.

Chronic systemic pesticide exposure reproduces features of Parkinson's disease

Nat. Neurosci.

Leber's hereditary optic neuropathy: a model for mitochondrial neurodegenerative diseases

FASEB J.