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Title: Lasting retinal injury in a mouse model of blast-induced trauma

item MAMMADOVA, NAJIBA - Iowa State University
item SAKAGUCHI, DONALD - Iowa State University
item KANTHASAMY, ANUMANTHA - Iowa State University
item Greenlee, Justin
item WEST GREENLEE, M - Iowa State University

Submitted to: American Journal of Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/2/2017
Publication Date: 7/1/2017
Citation: Mammadova, N., Ghaisas, S., Zenitsky, G., Sakaguchi, D.S., Kanthasamy, A.G., Greenlee, J.J., West Greenlee, M.H. 2017. Lasting retinal injury in a mouse model of blast-induced trauma. American Journal of Pathology. 187(7):1459-1472. doi:10.1016/j.ajpath.2017.03.005.

Interpretive Summary: Traumatic brain injury (TBI) due to blast exposure is currently the most prevalent of war injuries. The eye is susceptible to similar injuries, and blast injuries may damage the retina, the nervous tissue at the back of the eye responsible for vision. Over 80% of military personnel suffering from TBI also exhibit symptoms of visual dysfunction. Blast injuries to the eye are poorly understood. Moreover, there is no animal model to study the mechanisms of retinal cell damage that could allow objective testing of strategies to prevent or treat blast trauma. The purpose of this work was to develop a mouse model to understand damage to the retina caused by repeated blast wave pressure. This study demonstrates that blast wave pressure induces chronic responses in retinal cells including inflammation, neuronal loss, and accumulation of phospho-tau protein, a protein that is a major component of the "tangles" present in the brains of patients with Alzheimer's and other neurodegenerative diseases. This mouse model of blast-induced retinal trauma provides insight into chronic retinal pathologies caused by blast wave pressure. This work will be of interest to researchers in the fields of traumatic brain injury, neurodegenerative diseases, and blast injury of the brain and eye. This work may have an impact on developing preventative measures or treatment protocols for blast injury.

Technical Abstract: Traumatic brain injury (TBI) due to blast exposure is currently the most prevalent of war injuries. While secondary ocular blast injuries due to flying debris are more common, primary ocular blast exposure has been reported among survivors of explosions, but with limited understanding of the resulting retinal pathologies. Blast wave pressure (BWP) of 120 ± 7 kPa causes damage to the brain in a rat model, however, the effects of BWP on the retina have not been well characterized. Using a compressed air-driven shock tube system, adult male and female C57BL/6 mice were exposed to blast wave pressure of 300 kPa (43.5 psi) per day for three successive days, and euthanized 30 days post injury. We assessed retinal tissues using immunofluorescence, for glial fibrillary acidic protein (GFAP), microglia/macrophage specific protein Iba1, and phospho-PHF-tau (AT-270). Primary blast wave pressure resulted in activation of Müller glia, loss of photoreceptor cells, and expression of phospho-tau in the outer plexiform layer. Additionally, we observe activation of microglia based on an increase in Iba1 immunoreactivity and CD68 immunoreactivity. These changes were detected 30 days after blast exposure, suggesting the possibility of chronic retinal injury and neuronal inflammation after primary blast exposure.