Axonopathy precedes cell death in ocular damage mediated by blast exposure

Sci Rep. 2021 Jun 3;11(1):11774. doi: 10.1038/s41598-021-90412-2.


Traumatic brain injuries (TBI) of varied types are common across all populations and can cause visual problems. For military personnel in combat settings, injuries from blast exposures (bTBI) are prevalent and arise from a myriad of different situations. To model these diverse conditions, we are one of several groups modeling bTBI using mice in varying ways. Here, we report a refined analysis of retinal ganglion cell (RGC) damage in male C57BL/6J mice exposed to a blast-wave in an enclosed chamber. Ganglion cell layer thickness, RGC density (BRN3A and RBPMS immunoreactivity), cellular density of ganglion cell layer (hematoxylin and eosin staining), and axon numbers (paraphenylenediamine staining) were quantified at timepoints ranging from 1 to 17-weeks. RNA sequencing was performed at 1-week and 5-weeks post-injury. Earliest indices of damage, evident by 1-week post-injury, are a loss of RGC marker expression, damage to RGC axons, and increase in glial markers expression. Blast exposure caused a loss of RGC somas and axons-with greatest loss occurring by 5-weeks post-injury. While indices of glial involvement are prominent early, they quickly subside as RGCs are lost. The finding that axonopathy precedes soma loss resembles pathology observed in mouse models of glaucoma, suggesting similar mechanisms.

Publication types

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

MeSH terms

  • Animals
  • Axons / metabolism
  • Biomarkers
  • Blast Injuries / complications*
  • Brain Injuries, Traumatic / complications*
  • Brain Injuries, Traumatic / etiology*
  • Cell Death
  • Disease Models, Animal
  • Gene Expression Profiling
  • Mice
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Time Factors
  • Tomography, Optical Coherence
  • Vision Disorders / diagnosis
  • Vision Disorders / etiology*
  • Vision Disorders / metabolism


  • Biomarkers