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S.A. Croes, L.M. Baryshnikova, S.S. Kaluskar, C.S. von Bartheld; Long–term Effects of Botulinum Neurotoxin on the Function and Structure of Developing Extraocular Muscles . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5396.
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Botulinum neurotoxin (BTX) is used as an effective therapy for strabismus. BTX transiently abolishes neurotransmission, and its effects in skeletal muscle are reversible. In extraocular muscle (EOM) however, and in immature muscles in particular, BTX can have permanent therapeutic effects. The precise mechanisms of these effects have been elusive. There seems to be a specific long–term effect on orbital EOM fibers (Spencer and McNeer, 1987, Arch Ophthalmol 105:1703–11).
Here we examined effects of BTX in developing superior oblique muscles of chickens by a comprehensive analysis that included force measurements, myofiber morphometry, innervation, and quantitative transmission electron microscopy (TEM). Data were obtained at 2, 7, 14, 21, 28, 48, 56, and 77 days after injection of 0.25 or 0.5 ng BTX into the orbit of hatchling chicks, at an age that corresponds to the first months in humans, the preferred age of correction of infantile strabismus.
Contractile Force: Twitch tension, tetanic tension, and contraction time returned to normal within 56 days for the 0.25 ng dose. All parameters returned to normal by day 77 for the 0.5 ng dose except for twitch tension, which was still reduced by about 15%. Muscle morphometry: Myofiber diameters were normal through day 28, but were temporarily reduced in both orbital and global layers (48–56 days). Neuromuscular junctions: Terminal sprouts and new motor endplates were evident by day 14, however the size of the original singly–innervated endplates remained normal. TEM: By day 14 the fractional area of mitochondria was reduced and displayed an unusual distribution pattern, which both seem to persist to day 77.
(1) In developing EOMs, impairment of contractile forces is dose–dependent and long–term, but not permanent, with twitch tension specifically affected long term. (2) Changes in fiber diameter (muscle mass) as well as force efficiency contribute to the functional changes. (3) Long–term structural alterations are not confined to the orbital muscle fibers. (4) These data suggest that EOMs do not fully recover from BTX until they are nearly mature.
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