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P. Hahn, Y. Song, S. Grieco, M. A. Pook, J. L. Dunaief; Photoreceptor Degeneration in a Mouse Model of Friedreich Ataxia. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4498.
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Friedreich ataxia is the most common hereditary ataxia characterized by autosomal recessive inheritance of an unstable GAA repeat cluster, resulting in decreased expression of the protein frataxin. Among its putative functions, the mitochondrial protein frataxin is believed to be involved in iron metabolism possibly through its role in iron-sulfur cluster biogenesis. Decreased frataxin expression results in increased mitochondrial iron with increased oxidative stress. The purpose of this study was to determine if a mouse model of Friedriech ataxia might have alterations in retinal iron or iron- associated proteins or have associated retinal pathology.
Previously described frataxin-null C57BL/6 mice with a YAC transgene containing a human frataxin GAA repeat expansion were studied. Retinas from mice of different ages were analyzed with histology, immunohistochemistry, electron microscopy, and iron quantification using atomic absorption spectrophotometry.
Frataxin-altered mice demonstrate an age-related photoreceptor degeneration such that by 6 months of age there is >50% reduction in thickness of the outer nuclear layer with near complete loss of photoreceptors by age 18 months. We were unable to detect any changes in iron or iron-associated proteins.
Changes in frataxin levels are associated with an age-related photoreceptor degeneration in mice. The frataxin protein is believed to be involved in mitochondrial iron homeostasis, and this degeneration may result from alterations in iron trafficking. Future studies will be directed at understanding the mechanisms of this degeneration.
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