Several hypotheses have been put forward to explain EOM overaction.
26 These include one or more of the following: increased innervation; an increase in muscle cross-sectional area, both in individual fibers and total muscle cross sections; and/or changes in expression of individual myosin heavy chain isoforms. However, the actual state of the muscle in these patients is not understood. In the present study, in muscles of patients with strabismus who have overacting MR, there was an increase in the total number of satellite cells, but a decrease in the number of activated satellite cells, based on the number of myofibers. Of interest, in patients with a diagnosis of overacting inferior oblique muscles, there was a significant increase in satellite cells but there were also increases in activated satellite cells, as evidenced by an increase in MyoD-positive cells.
30 This difference may be the direct result of the differences in the etiology of inferior oblique and MR overaction.
26 In fact, when the eye is in the adducted position, inferior oblique muscle overelevation may be correlated to a possible hypoinnervation of the elevators of the eyes, especially the superior rectus. The inferior oblique, consequently, appears to be overactive when in reality it is not. It has been shown that patterns of nerve activation have significant effects on satellite cells in muscle. Previous studies have demonstrated that alterations in stimulation parameters result in an elevated number of satellite cells in the stimulated muscles.
31 In these muscles of patients with strabismus, it is not possible to determine whether these alterations are primary—that is, within the muscle itself—or secondary, due to changes in pattern of stimulation or alterations in innervation. However, the difference in the number of activated satellite cells in the “overacting” MR compared with the normal control muscles suggests several testable hypotheses. One possibility is that the reduction in the number of activated satellite cells may mean that the rate at which these cells fuse into fibers increases, being pushed by their environment into more rapid differentiation. This increase in fusion could be the result of a significant change in electrical stimulation from the oculomotor nerve. Changes in the pattern of electric stimulation is a known determinant of myogenic regulatory factor expression.
32 33 It is also possible that there is a reduced number of MyoD-positive satellite cells in the overacting muscles due to increased apoptosis of these cells. Muscle precursor cells often respond to removal of muscle growth factors by serum deprivation in vitro, for example, by either increased differentiation or apoptosis.
34 Both of these processes may occur simultaneously. Further studies are ongoing to distinguish between these possibilities.