PMID- 30703361
OWN - NLM
STAT- MEDLINE
DCOM- 20200221
LR  - 20200221
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 314
DP  - 2019 Apr
TI  - Retinoid x receptor modulation protects against ER stress response and rescues 
      glaucoma phenotypes in adult mice.
PG  - 111-125
LID - S0014-4886(18)30333-9 [pii]
LID - 10.1016/j.expneurol.2019.01.015 [doi]
AB  - Retinoid X receptors (RXRs) play an important role in transcription, are involved 
      in numerous cellular networks from cell proliferation to lipid metabolism and are 
      essential for normal eye development. RXRs form homo or heterodimers with other 
      nuclear receptors, bind to DNA response elements and regulate several biological 
      processes including neurogenesis. Mounting evidence suggests that RXR activation 
      by selective RXR modulators (sRXRms) may be neuroprotective in the central 
      nervous system. However, their potential neuroprotective role in the retina and 
      specifically in glaucoma remains unexplored. This study investigated changes in 
      RXR expression in the human and mouse retina under glaucomatous stress conditions 
      and investigated the effect of RXR modulation on the RGCs using pharmacological 
      approaches. RXR protein levels in retina were downregulated in both human 
      glaucoma and experimental RGC injury models while RXR agonist, bexarotene 
      treatment resulted in upregulation of RXR expression particularly in the inner 
      retinal layers. Retinal electrophysiological recordings and histological analysis 
      indicated that inner retinal function and retinal laminar structure were 
      preserved upon treatment with bexarotene. These protective effects were 
      associated with downregulation of ER stress marker response upon bexarotene 
      treatment under glaucoma conditions. Overall, retinal RXR modulation by 
      bexarotene significantly protected RGCs in vivo in both acute and chronic 
      glaucoma models.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Dheer, Yogita
AU  - Dheer Y
AD  - Faculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology 
      Place, North Ryde, NSW 2109, Australia. Electronic address: 
      yogita.dheer@hdr.mq.edu.au.
FAU - Chitranshi, Nitin
AU  - Chitranshi N
AD  - Faculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology 
      Place, North Ryde, NSW 2109, Australia.
FAU - Gupta, Veer
AU  - Gupta V
AD  - School of Medicine, Deakin University, Melbourne, Australia.
FAU - Sharma, Samridhi
AU  - Sharma S
AD  - Faculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology 
      Place, North Ryde, NSW 2109, Australia.
FAU - Pushpitha, Kanishka
AU  - Pushpitha K
AD  - Faculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology 
      Place, North Ryde, NSW 2109, Australia.
FAU - Abbasi, Mojdeh
AU  - Abbasi M
AD  - Faculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology 
      Place, North Ryde, NSW 2109, Australia.
FAU - Mirzaei, Mehdi
AU  - Mirzaei M
AD  - Department of Molecular Science, Macquarie University, North Ryde, NSW 2109, 
      Australia.
FAU - You, Yuyi
AU  - You Y
AD  - Save Sight Institute, Sydney University, Sydney, NSW 2000, Australia.
FAU - Graham, Stuart L
AU  - Graham SL
AD  - Faculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology 
      Place, North Ryde, NSW 2109, Australia; Save Sight Institute, Sydney University, 
      Sydney, NSW 2000, Australia.
FAU - Gupta, Vivek
AU  - Gupta V
AD  - Faculty of Medicine and Health Sciences, Macquarie University, F10A, 2 Technology 
      Place, North Ryde, NSW 2109, Australia. Electronic address: 
      vivek.gupta@mq.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190128
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Retinoid X Receptors)
RN  - A61RXM4375 (Bexarotene)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging
MH  - Animals
MH  - Bexarotene/*pharmacology/*therapeutic use
MH  - Electroretinography
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Female
MH  - Gene Expression/drug effects
MH  - Glaucoma/pathology/*prevention & control
MH  - Histone Deacetylase Inhibitors/therapeutic use
MH  - Histone Deacetylases/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/*pharmacology/*therapeutic use
MH  - Phenotype
MH  - Retina/drug effects/metabolism/pathology
MH  - Retinoid X Receptors/*agonists/biosynthesis
OTO - NOTNLM
OT  - Apoptosis
OT  - Bexarotene
OT  - ER stress
OT  - Glaucoma
OT  - HDAC
OT  - Retinoid-X-receptor
EDAT- 2019/02/01 06:00
MHDA- 2020/02/23 06:00
CRDT- 2019/02/01 06:00
PHST- 2018/08/09 00:00 [received]
PHST- 2018/11/23 00:00 [revised]
PHST- 2019/01/22 00:00 [accepted]
PHST- 2019/02/01 06:00 [pubmed]
PHST- 2020/02/23 06:00 [medline]
PHST- 2019/02/01 06:00 [entrez]
AID - S0014-4886(18)30333-9 [pii]
AID - 10.1016/j.expneurol.2019.01.015 [doi]
PST - ppublish
SO  - Exp Neurol. 2019 Apr;314:111-125. doi: 10.1016/j.expneurol.2019.01.015. Epub 2019 
      Jan 28.