Activated satellite cells in extraocular muscles of normal adult monkeys and humans

PURPOSE. Mammalian extraocular muscles (EOMs) are both physiologically and biochemically unique when compared with nonocular skeletal muscles. Recent studies have demonstrated a process of continuous myonuclear addition in normal uninjured myofibers in adult EOMs of rabbits and mice. The current study was conducted to determine whether this process of myonuclear addition is a universal phenomenon in mammalian EOMs. METHODS. The EOMs from adult uninjured monkeys and humans were examined immunohistochemically for the expression of specific markers of activated satellite cells: hepatocyte growth factor (HGF); the myogenic regulatory factors MyoD, myogenin, and Pax7; and a marker for nuclei in all proliferative phases of the cell cycle, Ki-67. The satellite cell identity of the cells positive for Ki-67, HGF, and Pax7 was determined by colabeling sets of serial sections with either laminin or dystrophin. RESULTS. In cross sections of monkey and human EOMs, approximately 7% to 8% of the myofiber profiles were associated with Pax7-positive satellite cells and between 2% and 4% were associated with MyoD-positive satellite cells or HGF-positive satellite cells. Similar percentages of satellite cells were positive for myogenin in the orbital layer, but the global layer had few satellite cells that were myogenin positive. An average of 0.72% of the myofibers had Ki-67-positive cells associated with them in the satellite cell position. CONCLUSIONS. Activated satellite cells were present on myofibers in normal uninjured adult monkey and human EOMs, as visualized with these five distinct markers. The data support the hypothesis that the process of continuous myonuclear addition is most likely active in primate and human EOMs. The presence of continuous myofiber remodeling in EOM suggests new mechanisms that may be responsible for EOM sparing or involvement in skeletal muscle diseases.