Development of nystagmus with the absence of myod expression in the extraocular muscles

Laura L. Johnson, Rachel B Kueppers, Erin Y. Shen, Jolene C. Rudell, Linda K. McLoon

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


PURPOSE. Myoblast determination protein 1 (MYOD) is a critical myogenic regulatory factor in muscle development, differentiation, myofiber repair, and regeneration. As the extraocular muscles significantly remodel their myofibers throughout life compared with limb skeletal muscles, we hypothesized that the absence of MYOD would result in their abnormal structure and function. To assess structural and functional changes in the extraocular muscles in MyoD-/- mice, fiber size and number and optokinetic nystagmus reflex (OKN) responses were examined. METHODS. OKN was measured in MyoD-/- mice and littermate wild-type controls at 3, 6, and 12 months. The extraocular muscles were examined histologically for changes in mean myofiber cross-sectional area, total myofiber number, and nuclei immunostained for PAX7 and PITX2, markers of myogenic precursor cells. RESULTS. The MyoD-/- mice developed nystagmus, with both jerk and pendular waveforms, in the absence and in the presence of moving visual stimulation. At 12 months, there were significant losses in mean myofiber cross-sectional area and in total number of orbital layer fibers in all rectus muscles, as well as in global layer fibers in the superior and inferior rectus muscles. Haploinsufficient mice showed abnormal OKN responses. PITX2-positive cell entry into myofibers of the MyoD-/- mice was significantly reduced. CONCLUSIONS. This study is the first demonstration of the development of nystagmus in the constitutive absence of expression of the muscle-specific transcription factor MYOD. We hypothesize that myofiber loss over time may alter anterograde and/or retrograde communication between the motor nerves and extraocular muscles that are critical for maintaining normalcy of extraocular muscle function.

Original languageEnglish (US)
Article number3
JournalInvestigative Ophthalmology and Visual Science
Issue number13
StatePublished - Oct 2021

Bibliographical note

Funding Information:
Supported by grants from the National Institutes of Health (R01 EY15313 to LKM; P30 EY11375) and the National Eye Institute, National Institutes of Health (T32 5T32AR007612-19 to LLJ) and by the Minnesota Lions Foundation.

Publisher Copyright:
© 2021 Association for Research in Vision and Ophthalmology Inc.. All rights reserved.


  • Extraocular muscles
  • Morphometry
  • Nystagmus
  • Optokinetic nystagmus


Dive into the research topics of 'Development of nystagmus with the absence of myod expression in the extraocular muscles'. Together they form a unique fingerprint.

Cite this