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

Christy L. Willoughby, Jérome Fleuriet, Mark M. Walton, Michael J. Mustari, Linda K. McLoon

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3467-3483
Number of pages17
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number6
DOIs
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2015 The Association for Research in Vision and Ophthalmology, Inc.

Keywords

  • Brain-derived neurotrophic factor
  • Extraocular muscles
  • Myogenic growth factors
  • Strabismus

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