Neuroretinal Cell Death in a Murine Model of Closed Globe Injury: Pathological and Functional Characterization

Abstract

This is the only murine model of closed globe injury and the only model of retinal trauma with specific photoreceptor cell death. The clinical appearance mirrors that in severe retinal injury after blunt ocular trauma in humans, and the ultrastructural features are consistent with human and animal studies of commotio retinae. After ocular trauma, photoreceptor apoptosis may be prevented and visual outcomes improved by blocking of the cell death pathways.

Acute vitreoretinal trauma and inflammation after traumatic brain injury in mice

“…While we did not assess visual acuity in the bTBI mice, the loss of the photoreceptor layer observed would ultimately impair vision and this photoreceptor degeneration could mirror one of the mechanisms leading to vision loss seen in some human blast injuries 9. Additionally, photoreceptor damage and degeneration after direct blunt ocular trauma has been well documented in human34, 35 and animal models 36, 37, 38…”

Evaluation of Novel Polyunsaturated Fatty Acid Derived Lipid Mediators of Inflammation to Ameliorate the Deleterious Effects of Blast Over Pressure on Eye and Brain Visual Processing Centers in Rats

“…Improvement of our blast model in the future may also include looking at the visual system injury effects over a wide range of reasonable pressures (e.g., 10 -30 psi), repetitive blasts or combined primary and secondary insults (e.g., blast followed by weight drop induced skull-concussion). Others have shown that repetitive low level blasts, head concussions, or blunt force trauma to the eyes alone can lead to severe retinal degeneration in mice and rats (Blanch, 2012(Blanch, , 2014Tzekov, 2014;Choi, 2015).…”

“…Improvement of our blast model in the future may also include looking at the visual system injury effects over a wide range of reasonable pressures (e.g., 10 -30 psi), repetitive blasts or combined primary and secondary insults (e.g., blast followed by weight drop induced skull-concussion). Others have shown that repetitive low level blasts, head concussions, or blunt force trauma to the eyes alone can lead to severe retinal degeneration in mice and rats (Blanch, 2012(Blanch, , 2014Tzekov, 2014;Choi, 2015).Also, while behavioral impairments in visual acuity tracking reflex (i.e., optokinetics) have been looked at (Hines-Beard, 2012;Bricker-Anthony, 2014b), no one has attempted to translate the retinal injuries into actual loss of performance on vision dependent psychomotor tasks. Indeed, for blasted rats, we saw a 30% decrease in retinal signaling with a 2 and 3-fold more neuronal cell damage in their retinas and brain optic tracts, respectively; however, most rats still performed quite well on the visual discrimination task.…”

Compound 49b Reduces Inflammatory Markers and Apoptosis after Ocular Blast Injury

“…While the majority of the discussion in the work by Blanch [17] was focused on axotomy of retinal ganglion cells or the optic nerve, the findings are similar to our observations after exposure to ocular blast, with increased levels of inflammatory mediators and apoptotic rates. In a subsequent paper on retinal changes in a closed globe injury model, authors describe increased TUNEL labeling and apoptosis of photoreceptors in the retina, after injury was induced by firing an air gun pellet or ball bearing into the mouse eye [18] . In this model involving projectiles into the eye, photoreceptor apoptosis and necrosis were observed, but specific apoptotic proteins or inflammatory proteins were not investigated.…”