Blast Preconditioning Protects Retinal Ganglion Cells and Reveals Targets for Prevention of Neurodegeneration Following Blast-Mediated Traumatic Brian Injury
Autor: | Nickolas Boehme, Addison W. Woll, Dana A. Soukup, Alexander G. Bassuk, Abhigna Akurathi, Lucy P. Evans, Matthew M. Harper, Michael Delcau, Michael G. Anderson, Laura M. Dutca, Marco M. Hefti, Adam Hedberg-Buenz |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Retinal Ganglion Cells genetic structures Retinal ganglion Blast injury Retina 03 medical and health sciences Mice 0302 clinical medicine Kynurenine 3-Monooxygenase Blast Injuries Brain Injuries Traumatic medicine Electroretinography Animals kyneurinine-3-monooxygenase blast TBI retinal ganglion cell Nerve degeneration medicine.diagnostic_test business.industry Basic Local Alignment Search Tool Neurodegeneration Retinal Degeneration medicine.disease brain injury eye diseases Cell biology Structure and function Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure neuroprotection sense organs business 030217 neurology & neurosurgery Tomography Optical Coherence |
Zdroj: | Investigative Ophthalmology & Visual Science |
ISSN: | 1552-5783 0146-0404 |
Popis: | Purpose The purpose of this study was to examine the effect of multiple blast exposures and blast preconditioning on the structure and function of retinal ganglion cells (RGCs), to identify molecular pathways that contribute to RGC loss, and to evaluate the role of kynurenine-3-monooxygenase (KMO) inhibition on RGC structure and function. Methods Mice were subjected to sham blast injury, one single blast injury, or three blast injuries separated by either 1 hour or 1 week, using a blast intensity of 20 PSI. To examine the effect of blast preconditioning, mice were subjected to sham blast injury, one single 20-PSI injury, or three blast injuries separated by 1 week (5 PSI, 5 PSI, 20 PSI and 5 PSI, 5 PSI, 5 PSI). RGC structure was analyzed by optical coherence tomography (OCT) and function was analyzed by the pattern electroretinogram (PERG). BRN3A-positive cells were quantified to determine RGC density. RNA-seq analysis was used to identify transcriptional changes between groups. Results Analysis of mice with multiple blast exposures of 20 PSI revealed no significant differences compared to one 20-pounds per square inch (PSI) exposure using OCT, PERG, or BRN3A cell counts. Analysis of mice exposed to two preconditioning 5-PSI blasts prior to one 20-PSI blast showed preservation of RGC structure and function. RNA-seq analysis of the retina identified multiple transcriptomic changes between conditions. Pharmacologic inhibition of KMO preserved RGC responses compared to vehicle-treated mice. Conclusions Preconditioning protects RGC from blast injury. Protective effects appear to involve changes in KMO activity, whose inhibition is also protective. |
Databáze: | OpenAIRE |
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