Abstract
Abstract: :
Purpose: We recently demonstrated that there is a continuous process, albeit slow, of myonuclear addition into normal, uninjured adult myofibers in rabbit extraocular muscles (EOM) (McLoon and Wirtschafter, Muscle & Nerve, 2002). Many characteristics of mature rabbit EOM that make them distinct from non-ocular skeletal muscles are expressed in all mammalian EOM. These include continued expression of immature forms of myosin heavy chain isoform, neural cell adhesion molecule, and the immature form of the acetylcholine receptor. It is important to determine if the process of myonuclear addition into myofibers of uninjured, adult rabbit EOM also occurs in other species. Methods: The EOM from adult, uninjured monkeys and humans were examined for the expression of 3 specific markers of activated satellite cells, the muscle regulatory factors MyoD and Pax 7, and Ki-67, a marker for nuclei in the cell cycle. Results: Satellite cells positive for MyoD, Pax 7, and Ki-67 were found in all EOM cross-sections examined. For every 100 myofibers in cross-section, there were approximately 7 satellite cells positive for MyoD and 8 satellite cells positive for Pax-7. Ki-67-positive cells in the satellite cell location were much more sparse in the EOM cross-sections. Not surprisingly, 0.72 % of the myofibers had Ki-67-positive satellite cells associated with them. Conclusion: Activated satellite cells were present on myofibers in normal, uninjured adult human and monkey EOM as visualized with these 3 distinct markers. This data supports the hypothesis that the process of continuous myonuclear addition is most likely active in primate and human muscles. The existence of continuous myonuclear addition in adult, uninjured EOM fundamentally changes the accepted notion that these myofibers are postmitotic. There are appendicular skeletal muscle diseases that spare the EOM, including Duchenne muscular dystrophy, and there are also myopathic diseases that preferentially affect the EOM. Identification of the process of myonuclear addition in EOM provides a wealth of testable hypotheses for some long-standing enigmas involving their preferential sparing or involvement in various muscle diseases.
Keywords: 405 extraocular muscles: structure • 434 immunohistochemistry • 404 extraocular muscles: development