Blast Preconditioning Protects Retinal Ganglion Cells and Reveals Targets for Prevention of Neurodegeneration Following Blast-Mediated Traumatic Brian Injury

Matthew M Harper; Addison W Woll; Lucy P Evans; Michael Delcau; Abhigna Akurathi; Adam Hedberg-Buenz; Dana A Soukup; Nickolas Boehme; Marco M Hefti; Laura M Dutca; Michael G Anderson; Alexander G Bassuk

doi:10.1167/iovs.19-27565

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Blast Preconditioning Protects Retinal Ganglion Cells and Reveals Targets for Prevention of Neurodegeneration Following Blast-Mediated Traumatic Brian Injury

Journal article

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Peer reviewed

Blast Preconditioning Protects Retinal Ganglion Cells and Reveals Targets for Prevention of Neurodegeneration Following Blast-Mediated Traumatic Brian Injury

Matthew M Harper, Addison W Woll, Lucy P Evans, Michael Delcau, Abhigna Akurathi, Adam Hedberg-Buenz, Dana A Soukup, Nickolas Boehme, Marco M Hefti, Laura M Dutca, …

Investigative ophthalmology & visual science, Vol.60(13), pp.4159-4170

10/01/2019

DOI: 10.1167/iovs.19-27565

PMCID: PMC6785841

PMID: 31598627

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Abstract

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. 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. 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. Preconditioning protects RGC from blast injury. Protective effects appear to involve changes in KMO activity, whose inhibition is also protective.

Electroretinography

Retinal Ganglion Cells - physiology

Tomography, Optical Coherence

Kynurenine 3-Monooxygenase - pharmacology

Mice, Inbred C57BL

Retinal Degeneration - etiology

Blast Injuries - pathology

Retinal Ganglion Cells - pathology

Animals

Brain Injuries, Traumatic - pathology

Mice

Retinal Degeneration - pathology

Retinal Ganglion Cells - drug effects

Disease Models, Animal

Details

Title: Subtitle: Blast Preconditioning Protects Retinal Ganglion Cells and Reveals Targets for Prevention of Neurodegeneration Following Blast-Mediated Traumatic Brian Injury
Creators: Matthew M Harper - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
Addison W Woll - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
Lucy P Evans - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States
Michael Delcau - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
Abhigna Akurathi - The Iowa City Department of Veterans Affairs Medical Center, Center for the Prevention and Treatment of Visual Loss, Iowa City, Iowa
Adam Hedberg-Buenz - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, United States
Dana A Soukup - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, United States
Nickolas Boehme - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
Marco M Hefti - Department of Pathology, University of Iowa, Iowa City, Iowa, United States
Laura M Dutca - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
Michael G Anderson - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, United States
Alexander G Bassuk - Department of Neurology, University of Iowa, Iowa City, Iowa, United States
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.60(13), pp.4159-4170
DOI: 10.1167/iovs.19-27565
PMID: 31598627
PMCID: PMC6785841
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: P30 EY025580 / NEI NIH HHS IK2 RX002003 / RRD VA T32 GM007337 / NIGMS NIH HHS T32 DK112751 / NIDDK NIH HHS K23 NS109284 / NINDS NIH HHS I01 RX001481 / RRD VA KL2 TR002536 / NCATS NIH HHS
Language: English
Date published: 10/01/2019
Academic Unit: Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Biology; Neurology (Pediatrics); Ophthalmology and Visual Sciences
Record Identifier: 9984070599802771

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