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MT Pardue, T Barnett, MJ Phillips, V Biousse, P Allard, NJ Newman, DC Wallace; Ocular Characteristics of a Mouse Model of Mitochondrial Disease . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1775.
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Purpose: Mice genetically engineered to eliminate the first isoform of the adenine nucleotide translocator (ANT1) suffer from severe ATP defiency in muscle. This results in mitochondrial myopathy recognized by ragged red fibers, cardiac myopathy, and exercise intolerance1. ANT1 mutant mice were examined for ocular defects. Methods: 1) Using slit lamp biomicroscopy, the lens was examined in the mutant and age-matched controls. 2) To evaluate retinal function, ERGs were performed under dark- and light-adapted conditions in young (6 months) and old (16-24 month) mice. Data was compared to age-matched wild-type controls. 3) To examine retinal structure, eyes were processed into plastic, and sections were examined using light and electron microscopy. Results: ANT1 mice older than 12 months had both posterior and nuclear cataracts, similar to age-matched controls. ERG amplitudes and latencies for the ANT1 mutants were similar to age-matched controls for both the dark- and light-adapted conditions. Retinal structure appeared normal at the light microscopy level with no significant differences in retinal layer thickness. At the EM level, the mitochondria in the ANT1 retina appeared normal structurally, but were more numerous. Conclusion: While the ANT1 mutation results in a decrease in cytoplasmic ATP, the ANT1 eye does not show a decline in retinal function or retinal degeneration. This may be due to an upregulation of the other ANT isoform, ANT2, or due to some protective factor that spares function to the highly metabolic retina. Further analysis of the ANT1 mutant mice will focus on identifying other clinical mitochondrial phenotypes commonly found in the eye. 1Graham et al., 1997; Nature Gen. 16: 226-234
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