PMID- 33505775
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20210628
IS  - 2164-2591 (Electronic)
IS  - 2164-2591 (Linking)
VI  - 10
IP  - 1
DP  - 2021 Jan
TI  - RGC and Vision Loss From Traumatic Optic Neuropathy Induced by Repetitive Closed 
      Head Trauma Is Dependent on Timing and Force of Impact.
PG  - 8
LID - 10.1167/tvst.10.1.8 [doi]
LID - 8
AB  - PURPOSE: Traumatic optic neuropathy (TON) is often caused by blunt head trauma 
      and has no currently effective treatment. Common animal models of TON induced by 
      surgical crush injury are plagued by variability and do not mimic typical 
      mechanisms of TON injury. Traumatic head impact models have recently shown 
      evidence of TON, but the degree of head impact necessary to consistently induce 
      TON is not well characterized, and it is examined here. METHODS: Traumatic skull 
      impacts to C57BL/6J mice were induced using an electromagnetic controlled impact 
      device. One impact performed at two depths (mild and severe), as well as three 
      and five repetitive impacts with an interconcussion interval of 48 hours, were 
      tested. Optokinetic responses (OKRs) and retinal ganglion cell (RGC) loss were 
      measured. RESULTS: Five repetitive mild impacts significantly decreased OKR 
      scores and RGC numbers compared with control mice 10 weeks after initial impact, 
      with maximal pathology observed by 6 weeks and partial but significant loss 
      present by 3 weeks. One severe impact induced similar TON. Three mild impacts 
      also induced early OKR and RGC loss, but one mild impact did not. Equivalent 
      degrees of TON were induced bilaterally, and a significant correlation was 
      observed between OKR scores and RGC numbers. CONCLUSIONS: Repetitive, mild closed 
      head trauma in mice induces progressive RGC and vision loss that worsens with 
      increasing impacts. TRANSLATIONAL RELEVANCE: Results detail a reproducible model 
      of TON that provides a reliable platform for studying potential treatments over a 
      3- to 6-week time course.
CI  - Copyright 2021 The Authors.
FAU - Khan, Reas S
AU  - Khan RS
AD  - Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, 
      Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Ross, Ahmara G
AU  - Ross AG
AD  - Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, 
      Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
AD  - Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Aravand, Puya
AU  - Aravand P
AD  - Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, 
      Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Dine, Kimberly
AU  - Dine K
AD  - Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, 
      Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Selzer, Evan B
AU  - Selzer EB
AD  - Thomas Jefferson University School of Medicine, Philadelphia, PA, USA.
FAU - Shindler, Kenneth S
AU  - Shindler KS
AD  - Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, 
      Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA.
AD  - Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
LA  - eng
GR  - K08 EY030163/EY/NEI NIH HHS/United States
GR  - P30 EY001583/EY/NEI NIH HHS/United States
GR  - R01 EY019014/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210106
PL  - United States
TA  - Transl Vis Sci Technol
JT  - Translational vision science & technology
JID - 101595919
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - *Head Injuries, Closed/complications
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Optic Nerve Injuries
MH  - Retinal Ganglion Cells
PMC - PMC7794277
OTO - NOTNLM
OT  - retinal ganglion cell
OT  - traumatic head impact
OT  - traumatic optic neuropathy
COIS- Disclosure: R.S. Khan, None; A.G. Ross, None; P. Aravand, None; K. Dine, None; 
      E.B. Selzer, None; K.S. Shindler, None
EDAT- 2021/01/29 06:00
MHDA- 2021/06/29 06:00
PMCR- 2021/01/06
CRDT- 2021/01/28 05:43
PHST- 2020/06/18 00:00 [received]
PHST- 2020/12/09 00:00 [accepted]
PHST- 2021/01/28 05:43 [entrez]
PHST- 2021/01/29 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/01/06 00:00 [pmc-release]
AID - TVST-20-2753 [pii]
AID - 10.1167/tvst.10.1.8 [doi]
PST - epublish
SO  - Transl Vis Sci Technol. 2021 Jan 6;10(1):8. doi: 10.1167/tvst.10.1.8. eCollection 
      2021 Jan.