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Linda K McLoon; Radiation Resistance and Muscle Stem Cells in Extraocular Muscles from a Mouse Model of Muscular Dystrophy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1396.
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© ARVO (1962-2015); The Authors (2016-present)
The extraocular muscles (EOM) are known to be spared in Duchenne and other forms of muscular dystrophy. Our data suggest that muscle stem cells in the EOM are responsible for this sparing. We previously showed that 18Gy irradiation of EOM in mdx:utrophin+/- mice resulted in the transient appearance of a dystrophic phenotype. However, by 2 months after the irradiation, the EOM returned to normal, suggesting a radiation-resistant muscle stem cell population within the EOM. To test this, we treated wild type and mdx:utrophin+/- mice with higher doses of gamma irradiation and assessed myofiber size, central nucleation, and muscle stem cell populations expressing either Pitx2 or Pax7.
The orbital region of wild type (WT) and mdx:utrophin+/- mice (het) were irradiated at 30Gy or two doses of 18Gy one month apart. At various post-irradiation time points, the irradiated EOM were frozen, sectioned, processed histologically, and examined for cross-sectional areas, central nucleation, and for density of Pax7 positive and Pitx2 positive muscle stem cells.
For both irradiation methods, central nucleation increased in the treated EOM at all the post-irradiation time points. There were no significant changes in mean myofiber cross-sectional area in the EOM subjected to two doses of 18Gy irradiation; however the orbital layer myofibers were significantly smaller 60 days after 30Gy irradiation. There was a small but significant reduction in total myofiber number after 30Gy irradiation and by 170 days after the two doses of 18Gy. These changes correlated with a significant decrease in the Pax7 but not the Pitx2 muscle stem cells. These data were in direct contrast to leg muscles treated similarly, which saw a significant reduction in both populations and a large loss in muscle mass.
These data support our hypothesis that the populations of muscle stem cells in the EOM play a role in their sparing from the pathological signs of muscular dystrophy. Higher doses of gamma irradiation had a differential role on the two main muscle stem cell populations, resulting in a mild but persistent appearance of dystrophic changes in the EOM from this mouse model of muscular dystrophy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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