PMID- 29148976
OWN - NLM
STAT- MEDLINE
DCOM- 20180625
LR  - 20181113
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 6
DP  - 2017 Nov 17
TI  - Small molecule Photoregulin3 prevents retinal degeneration in the Rho(P23H) mouse 
      model of retinitis pigmentosa.
LID - e30577 [pii]
LID - 10.7554/eLife.30577 [doi]
AB  - Regulation of rod gene expression has emerged as a potential therapeutic strategy 
      to treat retinal degenerative diseases like retinitis pigmentosa (RP). We 
      previously reported on a small molecule modulator of the rod transcription factor 
      Nr2e3, Photoregulin1 (PR1), that regulates the expression of 
      photoreceptor-specific genes. Although PR1 slows the progression of retinal 
      degeneration in models of RP in vitro, in vivo analyses were not possible with 
      PR1. We now report a structurally unrelated compound, Photoregulin3 (PR3) that 
      also inhibits rod photoreceptor gene expression, potentially though Nr2e3 
      modulation. To determine the effectiveness of PR3 as a potential therapy for RP, 
      we treated Rho(P23H) mice with PR3 and assessed retinal structure and function. 
      PR3-treated Rho(P23H) mice showed significant structural and functional 
      photoreceptor rescue compared with vehicle-treated littermate control mice. These 
      results provide further support that pharmacological modulation of rod gene 
      expression provides a potential strategy for the treatment of RP.
FAU - Nakamura, Paul A
AU  - Nakamura PA
AUID- ORCID: 0000-0002-3845-8477
AD  - Department of Biological Structure, University of Washington, School of Medicine, 
      Seattle, United States.
FAU - Shimchuk, Andy A
AU  - Shimchuk AA
AD  - Department of Biological Structure, University of Washington, School of Medicine, 
      Seattle, United States.
FAU - Tang, Shibing
AU  - Tang S
AD  - Department of Pharmaceutical Chemistry, UCSF School of Pharmacy, University of 
      California, San Francisco, San Francisco, United States.
FAU - Wang, Zhizhi
AU  - Wang Z
AD  - Department of Biological Structure, University of Washington, School of Medicine, 
      Seattle, United States.
FAU - DeGolier, Kole
AU  - DeGolier K
AD  - Department of Biological Structure, University of Washington, School of Medicine, 
      Seattle, United States.
FAU - Ding, Sheng
AU  - Ding S
AD  - Department of Pharmaceutical Chemistry, UCSF School of Pharmacy, University of 
      California, San Francisco, San Francisco, United States.
FAU - Reh, Thomas A
AU  - Reh TA
AUID- ORCID: 0000-0002-3524-0886
AD  - Department of Biological Structure, University of Washington, School of Medicine, 
      Seattle, United States.
LA  - eng
GR  - P01 GM081619/GM/NIGMS NIH HHS/United States
GR  - P30 EY001730/EY/NEI NIH HHS/United States
GR  - R01 EY021374/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 - 20171117
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Nr2e3 protein, mouse)
RN  - 0 (Orphan Nuclear Receptors)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/*drug effects
MH  - Mice
MH  - Orphan Nuclear Receptors/*metabolism
MH  - Retinitis Pigmentosa/*drug therapy/*pathology
MH  - Treatment Outcome
PMC - PMC5693111
OTO - NOTNLM
OT  - ligand
OT  - mouse
OT  - neuroscience
OT  - photoreceptor dystrophy
OT  - retinal degeneration
COIS- No competing interests declared.
EDAT- 2017/11/18 06:00
MHDA- 2018/06/26 06:00
PMCR- 2017/11/17
CRDT- 2017/11/18 06:00
PHST- 2017/07/19 00:00 [received]
PHST- 2017/10/24 00:00 [accepted]
PHST- 2017/11/18 06:00 [entrez]
PHST- 2017/11/18 06:00 [pubmed]
PHST- 2018/06/26 06:00 [medline]
PHST- 2017/11/17 00:00 [pmc-release]
AID - e30577 [pii]
AID - 30577 [pii]
AID - 10.7554/eLife.30577 [doi]
PST - epublish
SO  - Elife. 2017 Nov 17;6:e30577. doi: 10.7554/eLife.30577.