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D. Vlachantoni, B. Tulloch, R.W. Taylor, D.M. Turnbull, M.P. Murphy, A.F. Wright; Effects of MitoQ and Sod2 on Rates of Retinal Degeneration in Rd1, Atrd1, Rho–/– and Rds Mutant Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5773.
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We previously proposed that rates of retinal degeneration are strongly influenced by constitutive reactive oxygen and nitrogen species (RONS) formation in mitochondria. We examine this proposal by crossing mice with different forms of retinal degeneration to a superoxide dismutase (Sod2) mutant line and by feeding the mitochondria–targeted antioxidant MitoQ, to try and influence rates of degeneration and oxidative damage.
: MitoQ was given orally to homozygous rd1, atrd1, rho –/–, Rds–/– and littermate controls from pregnancy until up to 4 months of age. Rates of degeneration were estimated from outer nuclear layer (ONL) thickness and TUNEL staining. Oxidative damage was measured indirectly by the ratio of activities of complex I (RONS–sensitive) to citrate synthase (RONS–insensitive) (CI/CS ratio) and glutathione assay.
MitoQ appears to be concentrated within the mitochondrial fraction of retina and other tissues but rates of retinal degeneration were unchanged either by MitoQ ingestion or on a Sod2+/– genetic background. A reduction in the CI/CS ratio was found in rd1, atrd1 and Rho–/– mice, indicating the presence of oxidative stress, which was ameliorated in mice fed MitoQ.
Rates of degeneration in mutant mice undergoing very rapid retinal degeneration are not influenced by MitoQ or Sod2, perhaps because the severity of the disease–associated stress is such that cell death is not readily reversed. It remains to be seen whether this is the case with slower acting mutations.
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