Acute and long-term effects of botulinum neurotoxin on the function and structure of developing extraocular muscles.
Strabismus is a misalignment of the visual axes, due to an imbalance in extraocular muscle (EOM) function. Botulinum neurotoxin (BoNT) treatment can correct the misalignment with permanent therapeutic effects in infants, possibly because the toxin causes structural alterations in developing EOM. To determine whether BoNT indeed permanently weakens developing EOMs, we examined the chicken oculomotor system. Following injections of BoNT in hatchling chicks, we quantified physiological parameters (contractile force measurements) and morphological parameters (myofiber morphometry, innervation, quantitative transmission electron microscopy of mitochondria/fiber types). Treatment of developing EOM with BoNT caused acute reductions of muscle strength and mitochondrial densities, but minimal changes in muscle fiber diameter and neuromuscular junction structures. Contrary to expectations, contractile force was fully recovered by 3-4 months after treatment. Thus, permanent therapeutic effects of BoNT most likely do not cause permanent changes at the level of the peripheral effector organ, but rather involve central (CNS) adaptive responses.
Croes
Scott A
SA
Department of Physiology and Cell Biology, Mailstop 352, University of Nevada School of Medicine, Reno, NV 89557, USA.
Baryshnikova
Larisa M
LM
Kaluskar
Soniya S
SS
von Bartheld
Christopher S
CS
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000633:toxicity*; D002642:Chick Embryo; D002645:Chickens; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009045:Motor Endplate / Q000187:drug effects / Q000473:pathology; D009119:Muscle Contraction / Q000187:drug effects; D018763:Muscle Fatigue / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D009801:Oculomotor Muscles / Q000187:drug effects* / Q000196:embryology / Q000473:pathology*; D020127:Recovery of Function; D013285:Strabismus / Q000188:drug therapy / Q000473:pathology
D009498:Neurotoxins; D019274:Botulinum Toxins, Type A