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X Zhang, D Jones, F Gonzalez-Lima; A Potential Model for Leber's Hereditary Optic Neuropathy: Rotenone Effects on Retinal Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):235.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The objective of this project is to create a toxicological mouse model of optic neuropathy caused by mitochondrial complex I dysfunction. This will be the first experimental model of optic neuropathy, and could be used to test candidate drug treatments for mitochondrial neurodegenerative diseases. Increasing evidence shows that Leber's hereditary optic neuropathy (LHON) is linked to mitochondrial complex I dysfunction. LHON is one of a group of neurodegenerative diseases, and it is regarded as a model disease for mitochondrial neurodegenerative diseases. Methods: To create a toxicological mouse model of LHON, intravitreal administration of rotenone, a mitochondrial complex I inhibitor, in CBA/J mice was performed with different animal survival times (non-injection, 0.5, 1, 24, 48 hours). Data of retinal thickness were collected from cross sections of retina which were stained histochemically with complex I enzymatic activity. Results: The thickness of the retinal ganglion cell layer of eyes injected with rotenone was significantly thinner than that of the control eyes injected with the vehicle DMSO at 1, 24, and 48-hour survival time groups. The largest reduction was 43% at 24-hour postinjection. The retinal inner plexiform layer of the rotenone treated eyes was also significantly thinner than that of the control eyes in the 24-hour group. There were no significant differences in the thickness of other retinal layers. Conclusion: The statistical evaluations of the model revealed that the thinning effect on the retina of the rotenone treated eye was due to the reduction of the thickness in the retinal ganglion cell layer and the inner plexiform layer, which contains mainly the dendrites of the retinal ganglion cells. This effect is consistent with the degeneration of retinal ganglion cells in LHON. This animal model may serve as a model for LHON as well as a potential model for mitochondrial dysfunction and neurodegeneration. The simplicity of the model provides a major advantage for its use as a quick and convenient way to screen candidate drug treatments.
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