July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
In Vivo Retinal Imaging of Post-Traumatic Neuroinflammation and Sequelae in Impact Concussion and Blast Exposure Mouse Models
Author Affiliations & Notes
  • Lee E Goldstein
    Boston University School of Medicine , Boston, Massachusetts, United States
    College of Engineering, Boston University, Boston, Massachusetts, United States
  • Olga Minaeva
    College of Engineering, Boston University, Boston, Massachusetts, United States
    Boston University School of Medicine , Boston, Massachusetts, United States
  • Mark Wojnarowicz
    Boston University School of Medicine , Boston, Massachusetts, United States
  • Juliet A Moncaster
    Boston University School of Medicine , Boston, Massachusetts, United States
  • Ivana Arellano
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Andrew M Fisher
    College of Engineering, Boston University, Boston, Massachusetts, United States
    Boston University School of Medicine , Boston, Massachusetts, United States
  • Erich S Franz
    College of Engineering, Boston University, Boston, Massachusetts, United States
    Boston University School of Medicine , Boston, Massachusetts, United States
  • R Daniel Ferguson
    Biomedical Optics, Physical Sciences, Inc, Andover, Massachusetts, United States
  • Mircea Mujat
    Biomedical Optics, Physical Sciences, Inc, Andover, Massachusetts, United States
  • Bertrand R Huber
    Boston University School of Medicine , Boston, Massachusetts, United States
    VA Boston Healthcare System, Boston, Massachusetts, United States
  • Anne B Fulton
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • James D Akula
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • David G Hunter
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
    Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Lee Goldstein, Rebion (C), Rebion (P), Rebion (I); Olga Minaeva, None; Mark Wojnarowicz, None; Juliet Moncaster, None; Ivana Arellano, None; Andrew Fisher, None; Erich Franz, None; R Ferguson, Physical Sciences, Inc (E); Mircea Mujat, Physical Sciences, Inc (E); Bertrand Huber, None; Anne Fulton, None; James Akula, None; David Hunter, Rebion (I), Rebion (P)
  • Footnotes
    Support  DoD W81XH-14-1-0592, Massachusetts Lions Eye Research Fund, Boston Children's Hospital Ophthalmology Foundation, Private Foundations
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5512. doi:
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      Lee E Goldstein, Olga Minaeva, Mark Wojnarowicz, Juliet A Moncaster, Ivana Arellano, Andrew M Fisher, Erich S Franz, R Daniel Ferguson, Mircea Mujat, Bertrand R Huber, Anne B Fulton, James D Akula, David G Hunter; In Vivo Retinal Imaging of Post-Traumatic Neuroinflammation and Sequelae in Impact Concussion and Blast Exposure Mouse Models. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5512.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Impact and blast neurotrauma induce post-traumatic microvasculopathy and neuroinflammation in brain and retina. Activation and interaction of specific immune cells are determinative of pacing and outcome post-injury. We investigated retinal cell imaging as a novel in vivo diagnostic technique for neuroaxis evaluation post-injury. We used new mouse models that recapitulate key features of acute concussion, mild traumatic brain injury (mTBI), and chronic traumatic encephalopathy (CTE) in humans.

Methods : Ccr2RFP/Cx3cr1GFP mice (Jackson Laboratory) enabled immune cell visualization by class (microglia, monocyte), origin (brain, retina, periphery), morphology, and location. Mouse models (matched for head kinematics): (i) closed-head impact injury (Tagge et al., Brain, 2018), (ii) blast exposure (Goldstein et al., Science Transl Med, 2012; Kondo et al., Nature, 2015). Mice were not anesthetized to enable acute neurobehavioral testing (Boston University Concussion Scale, BUCS). TBI-CTE histopathology, ultrastructure (EM), blood-brain/blood-retinal barrier function, immune cell imaging, electroretinography (ERG). Adaptive optics fluorescence scanning laser ophthalmoscope (AO-fSLO) with OCT imaging (Physical Sciences, Inc.).

Results : Impact-injured mice showed transient neurological impairment (contralateral hemiparesis, truncal ataxia, abnormal gait-balance), whereas blast-exposed mice did not. However, both experimental injuries induced axonopathy, microvasculopathy, monocyte infiltration, astrocytosis, microgliosis, and tau proteinopathy. BUCS scores did not correlate with structural, pathological, or functional endpoints. Before injury, Ccr2RFP/Cx3cr1GFP mice showed normal microglial distribution and phenotype in retina and brain. We detected focal microgliosis by in vivo retinal imaging that correlated with post-traumatic brain pathology. ERG analysis showed attenuated photoreceptor, postreceptor, and inner retinal responses post-injury.

Conclusions : Impact and blast neurotrauma induce distinct acute neurological responses but similar patterns of neuroinflammation, microvasculopathy, and functional sequelae in retina and brain. These results suggest that retinal cell imaging may be useful for noninvasive diagnosis, prognosis, staging, and monitoring of neurotrauma-related pathologies post-injury. Correlation with long-term TBI-CTE sequelae is underway.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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