Pathophysiology of blast‐induced ocular trauma in rats after repeated exposure to low‐level blast overpressure

Abstract

SBOP and RBOP induced retinal damage. RBOP caused more apoptosis in the optic nerve than SBOP, suggesting that RBOP causes more severe optic neuropathy than SBOP. SBOP and RBOP caused gliosis in the retina and increased inflammation in the optic nerve.

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).…”

“…First, we purposed to rigorously characterize the cellular, neuronal signaling, behavioral pathology of blast wave injuries to the eyes, specifically the retinas, and brain visual centers of adult male rats. These eye injury studies were more aptly carried out, in accordance with others, by subjecting the animals to high fidelity simulated blast over pressure waves (Friedlander waveform), as produced by a compressed air driven shock tube (Petras, 1997;Koliatsos, 2011;Wang, 2014;Choi, 2015). Eye and brain injuries are assessed by us in the rats out to 14 days post-exposure, using well established techniques of electroretinography (ERG; retinal signaling response with a light stimulus), visual discrimination behavioral testing (pressing a lever with a variable cue light to earn a food reward), and histopathology (H&E and silver stains for neuronal cell degeneration).…”

“…It is also possible that the brain visual centers are being directly affected, since it is well established that blast wave exposure causes traumatic brain injuries (Warden, 2006). Despite the difficult lifelong disability that permanent loss of vision represents, there are currently only a modest number of studies in animals that have attempted to assess blast wave injuries to the visual system (Petras, 1997;Koliatsos, 2011;HinesBeard, 2012;Jiang, 2013;Mohan, 2013;Zou, 2013;Bricker-Anthony, 2014a, b;Dutca, 2014;Wang, 2014;Bricker-Anthony, 2015;Choi, 2015). Many of these prior studies fall short on the soundness of experimental design (e.g., poor blast simulation and/or non-inclusive outcome measures); and only two have looked at potential drug treatments using agonists to the β-adrenergic receptor and nicotinamide phosphoribosyl transferase, as delivered by topical application to the cornea or systemically by intraperitoneal injection, respectively (Jiang, 2013;Dutca, 2014).…”

“…This implies that the majority of blast wave exposed soldiers may suffer some degree of retinal injuries, especially if their eyes are not protected. Additionally, we found that the brain visual processing centers of the blasted rats were damaged to an incidence of at least 53%; which is something to our knowledge that has not been clinically investigated in blast injured soldiers as an underlying pathological component for subsequent problems with vision loss.Retinal and brain visual center degeneration in rats has been previously produced by us and others using blast waves made by compressed air driven shock tubes, but was only proven by histopathology of the tissues (Petras, 1997;Koliatsos, 2011;Wang, 2014;Choi, 2015). Others have also observed retinal signaling deficits by ERG in conjunction with retinal cell damage by histopathology in mouse models of blast wave exposure (Hines-Beard, 2012;Jiang, 2013;Mohan, 2013; Bricker-Anthony, 2014a, b;Dutca, 2014;Bricker-Anthony, 2015); but the injury is unrealistically catastrophic (e.g., optic nerve avulsion) or delayed in manifestation (e.g., several months) due to very poor simulation of the blast waves.…”

“…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.…”