Molecular changes and vision loss in a mouse model of closed-globe blast trauma

Invest Ophthalmol Vis Sci. 2014 Jul 3;55(8):4853-62. doi: 10.1167/iovs.14-14353.


Purpose: To characterize retinal changes and assess vision after an eye-directed air blast.

Methods: Adult C57Bl/6 mice were exposed to a blast directed at one eye. Optical coherence tomography and histology were performed to assess retina and optic nerve integrity. Cell death, oxidative stress, and glial reactivity were examined by immunohistochemistry. Visual changes were measured by ERG recordings and the optokinetic reflex.

Results: In the outer retina, eye blast caused retinal pigment epithelium vacuoles and rare retinal detachments followed by regional cell death. Labeling for nitrotyrosine and markers of pyroptosis (caspase-1) and necroptosis (receptor-interacting protein kinases-1, -3) increased, primarily in the inner retina, after blast. Caspase-1 labeling was restricted primarily to the starburst amacrine cells. A few degenerating axons were detected at 28 days post blast. Despite a lack of substantial cell death or decreased ERG, there was a deficit in visual acuity after blast.

Conclusions: Oxidative stress, neuroinflammation, and cell death became increasingly prevalent, over time post blast suggestive of an ongoing neurodegenerative response. Outer retinal changes either resolved or remained focal. In contrast, inner retinal changes were more robust and spread from focal regions to the entire retina over time post blast. Our model of eye blast trauma causes molecular changes and a decrease in visual acuity within the first month post blast despite a lack of overt eye injury. This subtle response matches the delayed presentation of visual deficits in some blast-exposed Veterans.

Keywords: cell death pathways; oxidative stress; trauma; visual deficits.

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
  • Biomarkers / metabolism*
  • Blast Injuries / complications
  • Blast Injuries / diagnosis
  • Blast Injuries / metabolism*
  • Blindness / diagnosis
  • Blindness / etiology
  • Blindness / metabolism*
  • Cell Death
  • Disease Models, Animal
  • Electroretinography
  • Eye Injuries / complications
  • Eye Injuries / diagnosis
  • Eye Injuries / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Optic Nerve / metabolism
  • Optic Nerve / pathology
  • Oxidative Stress*
  • Retina / injuries
  • Retina / metabolism
  • Retina / pathology
  • Tomography, Optical Coherence
  • Visual Acuity*
  • Wounds, Nonpenetrating / complications
  • Wounds, Nonpenetrating / diagnosis
  • Wounds, Nonpenetrating / metabolism*


  • Biomarkers