Abstract
Abstract: :
Purpose: The extraocular muscles (EOM) are unique compared to limb skeletal muscles. They have extremely fast contractile properties, more complex myofiber types, and extremely small motor units. The most novel of these features is the presence of activated satellite cells within normal adult uninjured EOM, which become randomly and stably integrated into existing EOM myofibers. In order to elucidate potential mechanisms that might control this process, we examined the effects of a common treatment for strabismus, botulinum toxin A injection, on myonuclear addition and myofiber remodeling. Methods:One superior rectus muscle was injected intramuscularly with 5U of botulinum toxin A (BOTOX) (Allergan). The contralateral muscle received an injection of saline only. A second series of rabbits received a retrobulbar injection of BOTOX at a dose of 20U. To label dividing cells, rabbits received intraperitoneal injections of bromodeoxyuridine (brdU), a thymidine analogue, using a number of labeling time periods. After the appropriate interval, the rectus muscles were prepared for immunohistochemical localization of brdU–positive myonuclei and satellite cells using a double labeling method. Changes in brdU–positive myonuclei number were quantified. Results: When examined 14 days after a BOTOX injection, paralysis of the neuromuscular junctions resulted in a 2.5 fold increase in brdU–positive myonuclei and a 4.5 fold increase in brdU–positive satellite cells in the treated muscles compared to the contralateral control. By 21 days after a BOTOX injection, this short–term up–regulation of satellite cell division and myonuclear addition had decreased to the level seen in the contralateral muscles. Retrobulbar injection also resulted in a significant upregulation of myonuclear addition in the treated EOM. Conclusions:Extraocular muscle paralysis, as a result of BOTOX treatment, resulted in a significant short–term increase in myonuclear addition in single myofibers in adult rabbit EOM. Thus, normal muscle contraction must play a role in controlling this process in adult EOM. BOTOX is commonly used to treat paralytic strabismus. Understanding this effect of BOTOX on myonuclear addition and myofiber remodeling may suggest new ways to maximize the clinical effectiveness of BOTOX in strabismic patients.
Keywords: extraocular muscles: structure • strabismus • immunohistochemistry