An antibody to RGMa promotes regeneration of cochlear synapses after noise exposure

Sci Rep. 2021 Feb 3;11(1):2937. doi: 10.1038/s41598-021-81294-5.

Abstract

Auditory neuropathy is caused by the loss of afferent input to the brainstem via the components of the neural pathway comprising inner hair cells and the first order neurons of the spiral ganglion. Recent work has identified the synapse between cochlear primary afferent neurons and sensory hair cells as a particularly vulnerable component of this pathway. Loss of these synapses due to noise exposure or aging results in the pathology identified as hidden hearing loss, an initial stage of cochlear dysfunction that goes undetected in standard hearing tests. We show here that repulsive axonal guidance molecule a (RGMa) acts to prevent regrowth and synaptogenesis of peripheral auditory nerve fibers with inner hair cells. Treatment of noise-exposed animals with an anti-RGMa blocking antibody regenerated inner hair cell synapses and resulted in recovery of wave-I amplitude of the auditory brainstem response, indicating effective reversal of synaptopathy.

Publication types

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

MeSH terms

  • Acoustic Stimulation / methods
  • Animals
  • Auditory Threshold
  • Cochlea / cytology
  • Cochlea / drug effects
  • Cochlea / pathology
  • Disease Models, Animal
  • Female
  • GPI-Linked Proteins / antagonists & inhibitors*
  • GPI-Linked Proteins / metabolism
  • Hair Cells, Auditory, Inner / drug effects
  • Hearing Loss, Noise-Induced / drug therapy*
  • Hearing Loss, Noise-Induced / pathology
  • Humans
  • Male
  • Mice
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / metabolism
  • Regeneration / drug effects*
  • Synapses / drug effects
  • Synapses / pathology

Substances

  • GPI-Linked Proteins
  • Nerve Tissue Proteins
  • Rgma protein, mouse