Repetitive mild traumatic brain injury causes optic nerve and retinal damage in a mouse model

J Neuropathol Exp Neurol. 2014 Apr;73(4):345-61. doi: 10.1097/NEN.0000000000000059.


There is increasing evidence that long-lasting morphologic and functional consequences can be present in the human visual system after repetitive mild traumatic brain injury (r-mTBI). The exact location and extent of the damage in this condition are not well understood. Using a recently developed mouse model of r-mTBI, we assessed the effects on the retina and optic nerve using histology and immunohistochemistry, electroretinography (ERG), and spectral-domain optical coherence tomography (SD-OCT) at 10 and 13 weeks after injury. Control mice received repetitive anesthesia alone (r-sham). We observed decreased optic nerve diameters and increased cellularity and areas of demyelination in optic nerves in r-mTBI versus r-sham mice. There were concomitant areas of decreased cellularity in the retinal ganglion cell layer and approximately 67% decrease in brain-specific homeobox/POU domain protein 3A-positive retinal ganglion cells in retinal flat mounts. Furthermore, SD-OCT demonstrated a detectable thinning of the inner retina; ERG demonstrated a decrease in the amplitude of the photopic negative response without any change in a- or b-wave amplitude or timing. Thus, the ERG and SD-OCT data correlated well with changes detected by morphometric, histologic, and immunohistochemical methods, thereby supporting the use of these noninvasive methods in the assessment of visual function and morphology in clinical cases of mTBI.

Publication types

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

MeSH terms

  • Animals
  • Brain Injuries / complications*
  • Calcium-Binding Proteins / metabolism
  • Cell Count
  • Disease Models, Animal
  • Electroretinography
  • Female
  • Glial Fibrillary Acidic Protein / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism
  • Neurons / metabolism
  • Neurons / pathology
  • Optic Nerve Diseases / etiology*
  • Optic Nerve Diseases / pathology*
  • Retinal Diseases / etiology*
  • Retinal Diseases / pathology*
  • Time Factors
  • Tomography, Optical Coherence
  • Transcription Factor Brn-3A / metabolism


  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • Pou4f1 protein, mouse
  • Transcription Factor Brn-3A