PMID- 33764998
OWN - NLM
STAT- MEDLINE
DCOM- 20210831
LR  - 20210831
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 16
IP  - 3
DP  - 2021
TI  - Biomarkers of lesion severity in a rodent model of nonarteritic anterior ischemic 
      optic neuropathy (rNAION).
PG  - e0243186
LID - 10.1371/journal.pone.0243186 [doi]
LID - e0243186
AB  - The rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION) is 
      similar in many of its pathophysiological responses to clinical NAION. Like human 
      NAION, there is significant variability in the severity of the lesion produced, 
      and little is known of the parameters associated with rNAION induction severity 
      or if pre- or early post-induction biomarkers can be identified that enable 
      prediction of lesion severity and ultimate loss of retinal ganglion cells (RGCs). 
      Adult male Sprague-Dawley outbred rats were evaluated for various parameters 
      including physiological characteristics (heart rate, respiratory rate, 
      temperature, hematocrit [Hct]), optic nerve head (ONH) appearance, pre- and 
      post-induction mean diameter, and intravenous fluorescein and indocyanine green 
      angiographic patterns of vascular leakage at 5 hours post-induction, performed 
      using a spectral domain-optical coherence tomography (SD-OCT) instrument. Early 
      changes were correlated with ultimate RGC loss by Brn3a (+) immunohistology. RGC 
      loss also was correlated with the relative level of laser exposure. The severity 
      of ONH edema 2d, but not 5hr, post induction was most closely associated with the 
      degree of RGC loss, revealing a threshold effect, and consistent with a 
      compartment syndrome where a minimum level of capillary compression within a 
      tight space is responsible for damage. RGC loss increased dramatically as the 
      degree of laser exposure increased. Neither physiological parameters nor the 
      degree of capillary leakage 5hr post induction were informative as to the 
      ultimate degree of RGC loss. Similar to human NAION, the rNAION model exhibits 
      marked variability in lesion severity. Unlike clinical NAION, pre-induction ONH 
      diameter likely does not contribute to ultimate lesion severity; however, 
      cross-sectional ONH edema can be used as a biomarker 2d post-induction to 
      determine randomization of subjects prior to inclusion in specific 
      neuroprotection or neuroregeneration studies.
FAU - Guo, Yan
AU  - Guo Y
AD  - Department of Ophthalmology and Visual Sciences, University of Maryland at 
      Baltimore (UMB), Baltimore, Maryland, United States of America.
FAU - Mehrabian, Zara
AU  - Mehrabian Z
AD  - Department of Ophthalmology and Visual Sciences, University of Maryland at 
      Baltimore (UMB), Baltimore, Maryland, United States of America.
FAU - Johnson, Mary A
AU  - Johnson MA
AD  - Department of Ophthalmology and Visual Sciences, University of Maryland at 
      Baltimore (UMB), Baltimore, Maryland, United States of America.
FAU - Miller, Neil R
AU  - Miller NR
AD  - JHU Wilmer: Division of Neuro-Ophthalmology, Wilmer Eye Institute, Johns Hopkins 
      University School of Medicine, Baltimore, Maryland, United States of America.
FAU - Henderson, Amanda D
AU  - Henderson AD
AD  - JHU Wilmer: Division of Neuro-Ophthalmology, Wilmer Eye Institute, Johns Hopkins 
      University School of Medicine, Baltimore, Maryland, United States of America.
FAU - Hamlyn, John
AU  - Hamlyn J
AD  - Department of Physiology, UMB, Baltimore, Maryland, United States of America.
FAU - Bernstein, Steven L
AU  - Bernstein SL
AUID- ORCID: 0000-0001-7758-0136
AD  - Department of Ophthalmology and Visual Sciences, University of Maryland at 
      Baltimore (UMB), Baltimore, Maryland, United States of America.
AD  - Department of Anatomy and Neurobiology, UMB, Baltimore, Maryland, United States 
      of America.
LA  - eng
SI  - figshare/10.6084/m9.figshare.13643984
SI  - figshare/10.6084/m9.figshare.13644023
SI  - figshare/10.6084/m9.figshare.13644032
SI  - figshare/10.6084/m9.figshare.13644065
SI  - figshare/10.6084/m9.figshare.13644086
SI  - figshare/10.6084/m9.figshare.13644092
SI  - figshare/10.6084/m9.figshare.13644095
GR  - R01 EY015304/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 - 20210325
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (Transcription Factor Brn-3A)
SB  - IM
MH  - Angiography
MH  - Animals
MH  - Biomarkers/*analysis
MH  - Body Temperature
MH  - Disease Models, Animal
MH  - Heart Rate
MH  - Male
MH  - Optic Disk/anatomy & histology/diagnostic imaging
MH  - Optic Neuropathy, Ischemic/metabolism/*pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinal Ganglion Cells/metabolism/pathology
MH  - Severity of Illness Index
MH  - Transcription Factor Brn-3A/genetics/metabolism
PMC - PMC7993789
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/03/26 06:00
MHDA- 2021/09/01 06:00
PMCR- 2021/03/25
CRDT- 2021/03/25 17:24
PHST- 2020/11/15 00:00 [received]
PHST- 2021/02/28 00:00 [accepted]
PHST- 2021/03/25 17:24 [entrez]
PHST- 2021/03/26 06:00 [pubmed]
PHST- 2021/09/01 06:00 [medline]
PHST- 2021/03/25 00:00 [pmc-release]
AID - PONE-D-20-35932 [pii]
AID - 10.1371/journal.pone.0243186 [doi]
PST - epublish
SO  - PLoS One. 2021 Mar 25;16(3):e0243186. doi: 10.1371/journal.pone.0243186. 
      eCollection 2021.