Molecular Changes and Vision Loss in a Mouse Model of Closed-Globe Blast Trauma

Abstract

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.

Eye-Directed Overpressure Airwave-Induced Trauma Causes Lasting Damage to the Anterior and Posterior Globe: A Model for Testing Cell-Based Therapies

“…Retinal cell death was first detected at 1-month postblast and correlated with vision loss. 8,9 In contrast, in the posttrauma DBA/2J mouse eye, we found frequent severe anterior pathologies, larger retinal detachments with epiretinal membranes, immune infiltrate, increased oxidative stress, retinal cell death by 3 days postblast and more rapid and severe vision loss. 10 The DBA/2J lacks a fully functional anterior chamber-associated immune deviation, possibly explaining the greater injury response.…”

“…We have previously described the effects of this injury in the C57Bl/6J and DBA/2J mouse strains. 9,10 Upon visual examination, the eye of the C57Bl/6 mouse appears normal after this trauma, yet we detected small rare retinal detachments and increased oxidative stress beginning at 3 days posttrauma. Retinal cell death was first detected at 1-month postblast and correlated with vision loss.…”

“…We did not detect any degenerating axon profiles in the C57Bl/6J and the DBA/2J optic nerves until 28 days postinjury. 9,10 In contrast, the Balb/c optic nerves contained degenerating axons as early as 7 days postinjury. Traumatic optic neuropathy, which can occur after blast or blunt trauma, 6,13,14 is induced by 2 different injury mechanisms: primary (shearing of the axons and ischemia) and secondary (initial damage and death of the retinal ganglion cells).…”

“…1 Our laboratory developed and characterized a murine model of closed-globe eye trauma that recapitulates common injuries and vision loss observed in blast-exposed veterans. [8][9][10] The model produces an overpressure airwave (primary aspect of blast) directed at the mouse eye while the head and body are shielded. Thus, the model does not address additional injury that could be incurred due to free head movement or the tertiary aspect of blast trauma.…”

Acute vitreoretinal trauma and inflammation after traumatic brain injury in mice

“…Within the eye, blast trauma can cause injuries such as hyphema, retinal detachment, retinal edema, traumatic optic neuropathy, and loss of visual field 9, 11, 13, 32. Another mouse model of closed‐globe blast trauma directly applied to the eye saw a similarly delayed decrease in visual acuity, potentially due to the gradual increase in oxidative stress, neuroinflammation, and focal cell death 33. This delay in the progression of cell injury and death warrants further investigation, as early interventions could greatly improve visual outcomes for patients experiencing bTBI.…”