Abnormally small neuromuscular junctions in the extraocular muscles from subjects with idiopathic nystagmus and nystagmus associated with albinism

Linda K. McLoon, Christy L. Willoughby, Jill S. Anderson, Erick D. Bothun, David Stager, Joost Felius, Helena Lee, Irene Gottlob

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

PURPOSE. Infantile nystagmus syndrome (INS) is often associated with abnormalities of axonal outgrowth and connectivity. To determine if this manifests in extraocular muscle innervation, specimens from children with idiopathic INS or INS and albinism were examined and compared to normal age-matched control extraocular muscles. METHODS. Extraocular muscles removed during normal surgery on children with idiopathic INS or INS and albinism were immunostained for neuromuscular junctions, myofiber type, the immature form of the acetylcholine receptor, and brain-derived neurotrophic factor (BDNF) and compared to age-matched controls. RESULTS. Muscles from both the idiopathic INS and INS and albinism groups had neuromuscular junctions that were 35% to 71% smaller based on myofiber area and myofiber perimeter than found in age-matched controls, and this was seen on both fast and slow myosin heavy chain isoform–expressing myofibers (all P < 0.015). Muscles from subjects with INS and albinism showed a 7-fold increase in neuromuscular junction numbers on fast myofibers expressing the immature gamma subunit of the acetylcholine receptor. The extraocular muscles from both INS subgroups showed a significant increase in the number and size of slow myofibers compared to age-matched controls. Brain-derived neurotrophic factor was expressed in control muscle but was virtually absent in the INS muscles. CONCLUSIONS. These studies suggest that, relative to the final common pathway, INS is not the same between different patient etiologies. It should be possible to modulate these final common pathway abnormalities, via exogenous application of appropriate drugs, with the hope that this type of treatment may reduce the involuntary oscillatory movements in these children.

Original languageEnglish (US)
Pages (from-to)1912-1920
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume57
Issue number4
DOIs
StatePublished - Apr 1 2016

Bibliographical note

Funding Information:
Supported by National Institutes of Health Grants RO1 EY15313 (LKM) and P30 EY11375 from the National Eye Institute; the Minnesota Medical Foundation; the Minnesota Lions and Lionesses; and an unrestricted grant to the Department of Ophthalmology and Visual Neurosciences at the University of Minnesota from Research to Prevent Blindness, Inc. The authors alone are responsible for the content and writing of the paper.

Keywords

  • Acetylcholine receptor
  • Albinism
  • Extraocular muscles
  • Neuromuscular junction
  • Nystagmus

Fingerprint Dive into the research topics of 'Abnormally small neuromuscular junctions in the extraocular muscles from subjects with idiopathic nystagmus and nystagmus associated with albinism'. Together they form a unique fingerprint.

Cite this