July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Retina microglial activation and functional deficits in an impact concussion mouse model.of traumatic brain injury (TBI).
Author Affiliations & Notes
  • Lee E Goldstein
    Radiology, Boston University, Boston, Massachusetts, United States
  • Olga Minaeva
    Radiology, Boston University, Boston, Massachusetts, United States
  • Juliet A Moncaster
    Radiology, Boston University, Boston, Massachusetts, United States
  • Mark Wojnarowicz
    School of Medicine, Boston University, Massachusetts, United States
  • Erich Franz
    School of Medicine, Boston University, Massachusetts, United States
  • Mircea Mujat
    Physical Sciences Inc., Massachusetts, United States
  • R Daniel Ferguson
    Physical Sciences Inc., Massachusetts, United States
  • Ivana Arellano
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Lois E H Smith
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Anne B Fulton
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Bertrand R Huber
    School of Medicine, Boston University, Massachusetts, United States
  • David G Hunter
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • James D Akula
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Lee Goldstein, None; Olga Minaeva, None; Juliet Moncaster, None; Mark Wojnarowicz, None; Erich Franz, None; Mircea Mujat, Physical Sciences Inc. (E); R Ferguson, Physical Sciences Inc. (E); Ivana Arellano, None; Lois Smith, None; Anne Fulton, None; Bertrand Huber, None; David Hunter, None; James D Akula, None
  • 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 2019, Vol.60, 4408. doi:https://doi.org/
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    • Get Citation

      Lee E Goldstein, Olga Minaeva, Juliet A Moncaster, Mark Wojnarowicz, Erich Franz, Mircea Mujat, R Daniel Ferguson, Ivana Arellano, Lois E H Smith, Anne B Fulton, Bertrand R Huber, David G Hunter, James D Akula; Retina microglial activation and functional deficits in an impact concussion mouse model.of traumatic brain injury (TBI).. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4408. doi: https://doi.org/.

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

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Abstract

Purpose : Traumatic Brain Injury (TBI) induces brain inflammation characterized by reactive microgliosis, infiltration of peripheral monocytes, and pro- and anti-inflammatory molecules. These responses can either facilitate recovery or trigger sequelae. Activation and interaction of specific immune cells and phenotypes are determinative of temporal pacing and outcome of brain recovery after concussive head injury.

Methods : We utilized Ccr2RFP/Cx3cr1GFP mice (Jackson Laboratory) to enable immune cell visualization by class (microglia, monocyte), origin (peripheral, brain, retina), morphology, and location. We used a closed-head impact injury mouse model that recapitulates key features of human concussion. Experimental injury was conducted without anesthesia (approved IACUC protocol) to enable quantitative neurological assessment (Boston University Concussion Scale, BUCS). We evaluated histopathology, ultrastructural analysis, bloodbrain/retinal barrier function, immune cell imaging, and electrophysiology. We also used an adaptive optics fluorescence scanning laser ophthalmoscope (AO-fSLO) with OCT imaging (Physical Sciences, Inc.).

Results : Head-injured mice exhibited transient contralateral hemiparesis, truncal ataxia, impaired balance, and abnormal locomotion that recapitulated concussion in humans. We observed significant increase in microglia in retina and brain post-injury. Impact injury induced axonopathy, blood-brain barrier disruption, reactive astrocytosis and microgliosis, and peripheral monocyte infiltration in brain and retina.

Conclusions : Closed-head impact injury is associated with reactive inflammatory responses and sequelae in both retina and brain. The retina can be used as a “brain proxy” for noninvasive diagnosis, prognosis, staging and monitoring of neuroinflammation after closed-head injuries.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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