Eye alignment changes caused by sustained GDNF treatment of an extraocular muscle in infant non-human primates

Jérome Fleuriet, Christy L. Willoughby, Rachel B Kueppers, Michael J. Mustari, Linda K. McLoon

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The ability of sustained treatment of a single extraocular muscle with glial cell line-derived neurotrophic factor (GDNF) to produce a strabismus in infant non-human primates was tested. Six infant non-human primates received a pellet containing GDNF, releasing 2 µg/day for 90 days, on one medial rectus muscle. Eye alignment was assessed up to 6 months. Five of the six animals showed a slow decrease in eye misalignment from the significant exotropia present at birth, ending with approximately 10° of exotropia. Controls became orthotropic. Misalignment averaged 8° three months after treatment ended. After sustained GDNF treatment, few changes were seen in mean myofiber cross-sectional areas compared to age-matched naïve controls. Neuromuscular junction number was unaltered in the medial rectus muscles, but were significantly reduced in the untreated lateral recti. Neuromuscular junctions on slow fibers became multiply innervated after this sustained GDNF treatment. Pitx2-positive cells significantly decreased in treated and contralateral medial rectus muscles. Our study suggests that balanced GDNF signaling plays a role in normal development and maintenance of orthotropia. Sustained GDNF treatment of one medial rectus muscle resulted in a measurable misalignment largely maintained 3 months after treatment ended. Structural changes suggest mechanisms for producing an imbalance in muscle function.

Original languageEnglish (US)
Article number11927
JournalScientific reports
Volume10
Issue number1
DOIs
StatePublished - Jul 17 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

Keywords

  • Animals
  • Eye/drug effects
  • Female
  • Glial Cell Line-Derived Neurotrophic Factor/pharmacology
  • Haplorhini
  • Male
  • Muscle Development/drug effects
  • Neuromuscular Junction/drug effects
  • Oculomotor Muscles/innervation
  • Stem Cells/drug effects
  • Time Factors

PubMed: MeSH publication types

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

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