Adaptation of slow myofibers: the effect of sustained BDNF treatment of extraocular muscles in infant nonhuman primates

Invest Ophthalmol Vis Sci. 2015 Jun;56(6):3467-83. doi: 10.1167/iovs.15-16852.

Abstract

Purpose: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Ocular / physiology*
  • Adaptation, Physiological
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Delayed-Action Preparations
  • Disease Models, Animal
  • Macaca nemestrina
  • Mice
  • Muscle Fibers, Slow-Twitch / diagnostic imaging
  • Muscle Fibers, Slow-Twitch / drug effects*
  • Muscle Fibers, Slow-Twitch / metabolism
  • Myosins / metabolism
  • Neuromuscular Junction / drug effects
  • Oculomotor Muscles / diagnostic imaging
  • Oculomotor Muscles / drug effects*
  • Oculomotor Muscles / metabolism
  • Primates
  • Strabismus / physiopathology*
  • Ultrasonography

Substances

  • Brain-Derived Neurotrophic Factor
  • Delayed-Action Preparations
  • Myosins