PMID- 32180679
OWN - NLM
STAT- MEDLINE
DCOM- 20210204
LR  - 20210204
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 26
DP  - 2020
TI  - Endogenous Wnt/beta-catenin signaling in Muller cells protects retinal ganglion 
      cells from excitotoxic damage.
PG  - 135-149
AB  - PURPOSE: To analyze whether activation of endogenous wingless (Wnt)/beta-catenin 
      signaling in Muller cells is involved in protection of retinal ganglion cells 
      (RGCs) following excitotoxic damage. METHODS: Transgenic mice with a 
      tamoxifen-dependent beta-catenin deficiency in Muller cells were injected with 
      N-methyl-D-aspartate (NMDA) into the vitreous cavity of one eye to induce 
      excitotoxic damage of the RGCs, while the contralateral eye received PBS only. 
      Retinal damage was quantified by counting the total number of RGC axons in cross 
      sections of optic nerves and measuring the thickness of the retinal layers on 
      meridional sections. Then, terminal deoxynucleotidyl transferase dUTP nick-end 
      labeling (TUNEL) assay was performed to identify apoptotic cells in retinas of 
      both genotypes. Western blot analyses to assess the level of retinal beta-catenin 
      and real-time RT-PCR to quantify the retinal expression of neuroprotective 
      factors were performed. RESULTS: Following NMDA injection of wild-type mice, a 
      statistically significant increase in retinal beta-catenin protein levels was 
      observed compared to PBS-injected controls, an effect that was blocked in mice 
      with a Muller cell-specific beta-catenin deficiency. Furthermore, in mice with a 
      beta-catenin deficiency in Muller cells, NMDA injection led to a statistically 
      significant decrease in RGC axons as well as a substantial increase in 
      TUNEL-positive cells in the RGC layer compared to the NMDA-treated controls. 
      Moreover, in the retinas of the control mice a NMDA-mediated statistically 
      significant induction of leukemia inhibitory factor (Lif) mRNA was detected, an 
      effect that was substantially reduced in mice with a beta-catenin deficiency in 
      Muller cells. CONCLUSIONS: Endogenous Wnt/beta-catenin signaling in Muller cells 
      protects RGCs against excitotoxic damage, an effect that is most likely mediated 
      via the induction of neuroprotective factors, such as Lif.
CI  - Copyright (c) 2020 Molecular Vision.
FAU - Boesl, Fabian
AU  - Boesl F
AD  - Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, 
      Germany.
FAU - Drexler, Konstantin
AU  - Drexler K
AD  - Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, 
      Germany.
FAU - Muller, Birgit
AU  - Muller B
AD  - Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, 
      Germany.
FAU - Seitz, Roswitha
AU  - Seitz R
AD  - Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, 
      Germany.
FAU - Weber, Gregor R
AU  - Weber GR
AD  - Department of Ophthalmology, University Hospital, Ludwig-Maximilians-University 
      Munich, Germany.
FAU - Priglinger, Siegfried G
AU  - Priglinger SG
AD  - Department of Ophthalmology, University Hospital, Ludwig-Maximilians-University 
      Munich, Germany.
FAU - Fuchshofer, Rudolf
AU  - Fuchshofer R
AD  - Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, 
      Germany.
FAU - Tamm, Ernst R
AU  - Tamm ER
AD  - Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, 
      Germany.
FAU - Ohlmann, Andreas
AU  - Ohlmann A
AD  - Department of Ophthalmology, University Hospital, Ludwig-Maximilians-University 
      Munich, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200305
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (Leukemia Inhibitory Factor)
RN  - 0 (beta Catenin)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 6384-92-5 (N-Methylaspartate)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Axons/drug effects/metabolism
MH  - Ependymoglial Cells/drug effects/*metabolism
MH  - In Situ Nick-End Labeling
MH  - Leukemia Inhibitory Factor/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - N-Methylaspartate/toxicity
MH  - Optic Nerve/drug effects/*metabolism
MH  - Retina/drug effects/*metabolism/pathology
MH  - Retinal Ganglion Cells/drug effects/*metabolism
MH  - Tamoxifen/*pharmacology
MH  - Wnt Signaling Pathway/*drug effects/genetics
MH  - beta Catenin/deficiency/*metabolism
PMC - PMC7058433
EDAT- 2020/03/18 06:00
MHDA- 2021/02/05 06:00
PMCR- 2020/01/01
CRDT- 2020/03/18 06:00
PHST- 2019/08/01 00:00 [received]
PHST- 2020/03/03 00:00 [accepted]
PHST- 2020/03/18 06:00 [entrez]
PHST- 2020/03/18 06:00 [pubmed]
PHST- 2021/02/05 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 12 [pii]
PST - epublish
SO  - Mol Vis. 2020 Mar 5;26:135-149. eCollection 2020.