---
_id: '7033'
abstract:
- lang: eng
  text: Removal of the Bax gene from mice completely protects the somas of retinal
    ganglion cells (RGCs) from apoptosis following optic nerve injury. This makes
    BAX a promising therapeutic target to prevent neurodegeneration. In this study,
    Bax+/− mice were used to test the hypothesis that lowering the quantity of BAX
    in RGCs would delay apoptosis following optic nerve injury. RGCs were damaged
    by performing optic nerve crush (ONC) and then immunostaining for phospho-cJUN,
    and quantitative PCR were used to monitor the status of the BAX activation mechanism
    in the months following injury. The apoptotic susceptibility of injured cells
    was directly tested by virally introducing GFP-BAX into Bax−/− RGCs after injury.
    The competency of quiescent RGCs to reactivate their BAX activation mechanism
    was tested by intravitreal injection of the JNK pathway agonist, anisomycin. Twenty-four
    weeks after ONC, Bax+/− mice had significantly less cell loss in their RGC layer
    than Bax+/+ mice 3 weeks after ONC. Bax+/− and Bax+/+ RGCs exhibited similar patterns
    of nuclear phospho-cJUN accumulation immediately after ONC, which persisted in
    Bax+/− RGCs for up to 7 weeks before abating. The transcriptional activation of
    BAX-activating genes was similar in Bax+/− and Bax+/+ RGCs following ONC. Intriguingly,
    cells deactivated their BAX activation mechanism between 7 and 12 weeks after
    crush. Introduction of GFP-BAX into Bax−/− cells at 4 weeks after ONC showed that
    these cells had a nearly normal capacity to activate this protein, but this capacity
    was lost 8 weeks after crush. Collectively, these data suggest that 8–12 weeks
    after crush, damaged cells no longer displayed increased susceptibility to BAX
    activation relative to their naïve counterparts. In this same timeframe, retinal
    glial activation and the signaling of the pro-apoptotic JNK pathway also abated.
    Quiescent RGCs did not show a timely reactivation of their JNK pathway following
    intravitreal injection with anisomycin. These findings demonstrate that lowering
    the quantity of BAX in RGCs is neuroprotective after acute injury. Damaged RGCs
    enter a quiescent state months after injury and are no longer responsive to an
    apoptotic stimulus. Quiescent RGCs will require rejuvenation to reacquire functionality.
acknowledgement: This work was supported by National Eye Institute grants R01 EY012223
  (RWN), R01 EY030123 (RWN), T32 EY027721 (Department of Ophthalmology and Visual
  Sciences, University of Wisconsin-Madison), and a Vision Science Core grant P30
  EY016665 (Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison),
  an unrestricted funding grant from Research to Prevent Blindness (Department of
  Ophthalmology and Visual Sciences, University of Wisconsin-Madison), the Frederick
  A. Davis Endowment (RWN), and the Mr. and Mrs. George Taylor Foundation (RWN).
article_processing_charge: No
article_type: original
author:
- first_name: RJ
  full_name: Donahue, RJ
  last_name: Donahue
- first_name: Margaret E
  full_name: Maes, Margaret E
  id: 3838F452-F248-11E8-B48F-1D18A9856A87
  last_name: Maes
  orcid: 0000-0001-9642-1085
- first_name: JA
  full_name: Grosser, JA
  last_name: Grosser
- first_name: RW
  full_name: Nickells, RW
  last_name: Nickells
citation:
  ama: Donahue R, Maes ME, Grosser J, Nickells R. BAX-depleted retinal ganglion cells
    survive and become quiescent following optic nerve damage. <i>Molecular Neurobiology</i>.
    2020;57(2):1070–1084. doi:<a href="https://doi.org/10.1007/s12035-019-01783-7">10.1007/s12035-019-01783-7</a>
  apa: Donahue, R., Maes, M. E., Grosser, J., &#38; Nickells, R. (2020). BAX-depleted
    retinal ganglion cells survive and become quiescent following optic nerve damage.
    <i>Molecular Neurobiology</i>. Springer Nature. <a href="https://doi.org/10.1007/s12035-019-01783-7">https://doi.org/10.1007/s12035-019-01783-7</a>
  chicago: Donahue, RJ, Margaret E Maes, JA Grosser, and RW Nickells. “BAX-Depleted
    Retinal Ganglion Cells Survive and Become Quiescent Following Optic Nerve Damage.”
    <i>Molecular Neurobiology</i>. Springer Nature, 2020. <a href="https://doi.org/10.1007/s12035-019-01783-7">https://doi.org/10.1007/s12035-019-01783-7</a>.
  ieee: R. Donahue, M. E. Maes, J. Grosser, and R. Nickells, “BAX-depleted retinal
    ganglion cells survive and become quiescent following optic nerve damage,” <i>Molecular
    Neurobiology</i>, vol. 57, no. 2. Springer Nature, pp. 1070–1084, 2020.
  ista: Donahue R, Maes ME, Grosser J, Nickells R. 2020. BAX-depleted retinal ganglion
    cells survive and become quiescent following optic nerve damage. Molecular Neurobiology.
    57(2), 1070–1084.
  mla: Donahue, RJ, et al. “BAX-Depleted Retinal Ganglion Cells Survive and Become
    Quiescent Following Optic Nerve Damage.” <i>Molecular Neurobiology</i>, vol. 57,
    no. 2, Springer Nature, 2020, pp. 1070–1084, doi:<a href="https://doi.org/10.1007/s12035-019-01783-7">10.1007/s12035-019-01783-7</a>.
  short: R. Donahue, M.E. Maes, J. Grosser, R. Nickells, Molecular Neurobiology 57
    (2020) 1070–1084.
date_created: 2019-11-18T14:18:39Z
date_published: 2020-02-01T00:00:00Z
date_updated: 2023-08-17T14:05:48Z
day: '01'
department:
- _id: SaSi
doi: 10.1007/s12035-019-01783-7
external_id:
  isi:
  - '000493754200001'
  pmid:
  - '31673950'
intvolume: '        57'
isi: 1
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035206/
month: '02'
oa: 1
oa_version: Submitted Version
page: 1070–1084
pmid: 1
publication: Molecular Neurobiology
publication_identifier:
  eissn:
  - 1559-1182
  issn:
  - 0893-7648
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: BAX-depleted retinal ganglion cells survive and become quiescent following
  optic nerve damage
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 57
year: '2020'
...