Abstract
Abstract: :
Purpose: Common strabismus procedures induce compensatory alterations in extraocular muscle (eom) that are thought to be due to changes in resting tension. Resection, for example, increases preload and induces hypertrophy. In this study, we investigate the role of myofiber remodeling and myonuclear addition in this hypertrophic response. Methods: A 6mm resection of one superior rectus muscle was performed in adult rabbits. One week after surgery, the rabbits were injected every 2 hours for 12 hours with bromodeoxyuridine (brdU). After 24 hours, the muscles were prepared for immunohistochemical examination of brdU–positive myonuclei and satellite cells, and these changes were quantified. Alterations in the expression patterns of neonatal and developmental myosin heavy chain isoforms (MyHC) were also quantified. Results: Muscle stretch induced by resection surgery resulted in a 10–fold increase in satellite cell division and myonuclear addition compared to the contralateral control muscles and compared to muscles from unoperated control rabbits. In the normal process of myonuclear addition in eom myofibers, only one new myonucleus is added to a single myofiber in a 24–hour period. In the resected muscle, the majority of reconstructed myofibers contained more than one brdU–positive myonucleus, with up to 5 new myonuclei added to a single myofiber within the 24 hour post–labeling period. This represents a significant up–regulation of the process of myofiber remodeling in the operated muscles. There was also a significant increase in the number of myofibers expressing the neonatal MyHC. There was no apparent correlation between fibers that expressed the neonatal MyHC and the location of brdU–positive myonuclei. Conclusions: Muscle stretch induced by resection surgery resulted in a significant short–term increase in myonuclear addition in individual myofibers within adult rabbit EOM, as well as a significant increase in neonatal MyHC expression. The lack of correlation between expression of neonatal MyHC and new myonuclei suggests that the mechanisms that control these two processes are distinct. These results suggest a potential mechanism for the hypertrophic response seen in eom following resection surgery, and may open new avenues for pharmacological manipulation of eom force generation.
Keywords: extraocular muscles: structure • strabismus: treatment • plasticity