Acute vitreoretinal trauma and inflammation after traumatic brain injury in mice

Abstract

ObjectiveLimited attention has been given to ocular injuries associated with traumatic brain injury (TBI). The retina is an extension of the central nervous system and evaluation of ocular damage may offer a less‐invasive approach to gauge TBI severity and response to treatment. We aim to characterize acute changes in the mouse eye after exposure to two different models of TBI to assess the utility of eye damage as a surrogate to brain injury.MethodsA model of blast TBI (bTBI) using a shock tube was compared to a lateral fluid percussion injury model (LFPI) using fluid pressure applied directly to the brain. Whole eyes were collected from mice 3 days post LFPI and 24 days post bTBI and were evaluated histologically using a hematoxylin and eosin stain.Results bTBI mice showed evidence of vitreous detachment in the posterior chamber in addition to vitreous hemorrhage with inflammatory cells. Subretinal hemorrhage, photoreceptor degeneration, and decreased cellularity in the retinal ganglion cell layer was also seen in bTBI mice. In contrast, eyes of LFPI mice showed evidence of anterior uveitis and subcapsular cataracts.InterpretationWe demonstrated that variations in the type of TBI can result in drastically different phenotypic changes within the eye. As such, molecular and phenotypic changes in the eye following TBI may provide valuable information regarding the mechanism, severity, and ongoing pathophysiology of brain injury. Because vitreous samples are easily obtained, molecular changes within the eye could be utilized as biomarkers of TBI in human patients.

Traumatic chorioretinitis sclopetaria: Risk factors, management, and prognosis

“…Therefore, only a high velocity projectile, such as a bullet, passing adjacent to the globe, could create the shock wave forces that could produce retraction of both the retina and choroid, leaving bare sclera at the site of a break. 28 …”

“…The retina and choroid were replaced with dense and loose fibrous tissue respectively. Most recently, photoreceptor degeneration and decreased cellularity in the retinal ganglion cell layer have been demonstrated in mouse models following blast traumatic brain injury 28 …”

Sex Does Not Influence Visual Outcomes After Blast-Mediated Traumatic Brain Injury but IL-1 Pathway Mutations Confer Partial Rescue

“… 17 The increase in retinal inflammation after bTBI is documented in animal studies; nevertheless, how inflammation causes retinal pathogenesis is not well defined. 18 – 20 …”

“…In murine bTBI models, many groups (including ours) have found long-term deficits and cell death; most studies have focused particularly on the dysfunction and loss of retinal ganglion cell (RGCs). 18 – 24 RGC damage can permanently impair vision, resulting in major quality-of-life consequences; yet, the mechanisms responsible for bTBI-induced RGC dysfunction are not well understood. In recent experiments, the IL-1 pathway was pharmacologically blocked after bTBI to test whether acutely modulating this inflammatory IL-1 signaling might prevent subsequent neuronal deficits.…”

Identification of chronic brain protein changes and protein targets of serum auto-antibodies after blast-mediated traumatic brain injury

“…The pathophysiology of blastmediated TBI is precipitated by the interaction of a blast wave with neuronal tissue. Following this interaction, multiple mechanisms that lead to the death and dysfunction of neurons after exposure to TBI have been reported from several models [8,9,10]. These mechanisms include immediate [11,12,13] and delayed [14,15] neuronal changes.…”