title: Adaptation of slow myofibers: the effect of sustained BDNF treatment of extraocular muscles in infant nonhuman primates.
abstract: OBJECTIVE
  We evaluated promising new treatment options for strabismus. Neurotrophic factors have emerged as a potential treatment for oculomotor disorders because of diverse roles in signaling to muscles and motor neurons. Unilateral treatment with sustained release brain-derived neurotrophic factor (BDNF) to a single lateral rectus muscle in infant monkeys was performed to test the hypothesis that strabismus would develop in correlation with extraocular muscle (EOM) changes during the critical period for development of binocularity.
  
  
  METHODS
  The lateral rectus muscles of one eye in two infant macaques were treated with sustained delivery of BDNF for 3 months. Eye alignment was assessed using standard photographic methods. Muscle specimens were analyzed to examine the effects of BDNF on the density, morphology, and size of neuromuscular junctions, as well as myofiber size. Counts were compared to age-matched controls.
  
  
  RESULTS
  No change in eye alignment occurred with BDNF treatment. Compared to control muscle, neuromuscular junctions on myofibers expressing slow myosins had a larger area. Myofibers expressing slow myosin had larger diameters, and the percentage of myofibers expressing slow myosins increased in the proximal end of the muscle. Expression of BDNF was examined in control EOM, and observed to have strongest immunoreactivity outside the endplate zone.
  
  
  CONCLUSIONS
  We hypothesize that the oculomotor system adapted to sustained BDNF treatment to preserve normal alignment. Our results suggest that BDNF treatment preferentially altered myofibers expressing slow myosins. This implicates BDNF signaling as influencing the slow twitch properties of EOM.
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States 2Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States.
authors.forename: Christy L
authors.initials: CL
authors.lastname: Willoughby
authors.affiliation: Washington National Primate Research Center, Seattle, Washington, United States 4Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
authors.forename: Jérome
authors.initials: J
authors.lastname: Fleuriet
authors.affiliation: Washington National Primate Research Center, Seattle, Washington, United States.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Walton
authors.affiliation: Washington National Primate Research Center, Seattle, Washington, United States 4Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mustari
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States 2Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States.
authors.forename: Linda K
authors.initials: LK
authors.lastname: McLoon
mesh_terms: D000221:Adaptation, Ocular / Q000502:physiology*; D000222:Adaptation, Physiological; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D008254:Macaca nemestrina; D051379:Mice; D018657:Muscle Fibers, Slow-Twitch / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects; D009801:Oculomotor Muscles / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D011323:Primates; D013285:Strabismus / Q000503:physiopathology*; D014463:Ultrasonography
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003692:Delayed-Action Preparations; D009218:Myosins