PMID- 21940995
OWN - NLM
STAT- MEDLINE
DCOM- 20120227
LR  - 20240321
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 26
IP  - 1
DP  - 2012 Jan
TI  - Retinoid receptors trigger neuritogenesis in retinal degenerations.
PG  - 81-92
LID - 10.1096/fj.11-192914 [doi]
AB  - Anomalous neuritogenesis is a hallmark of neurodegenerative disorders, including 
      retinal degenerations, epilepsy, and Alzheimer's disease. The neuritogenesis 
      processes result in a partial reinnervation, new circuitry, and functional 
      changes within the deafferented retina and brain regions. Using the light-induced 
      retinal degeneration (LIRD) mouse model, which provides a unique platform for 
      exploring the mechanisms underlying neuritogenesis, we found that retinoid X 
      receptors (RXRs) control neuritogenesis. LIRD rapidly triggered retinal neuron 
      neuritogenesis and up-regulated several key elements of retinoic acid (RA) 
      signaling, including retinoid X receptors (RXRs). Exogenous RA initiated 
      neuritogenesis in normal adult retinas and primary retinal cultures and 
      exacerbated it in LIRD retinas. However, LIRD-induced neuritogenesis was partly 
      attenuated in retinol dehydrogenase knockout (Rdh12(-/-)) mice and by aldehyde 
      dehydrogenase inhibitors. We further found that LIRD rapidly increased the 
      expression of glutamate receptor 2 and beta Ca(2+)/calmodulin-dependent protein 
      kinase II (betaCaMKII). Pulldown assays demonstrated interaction between betaCaMKII and 
      RXRs, suggesting that CaMKII pathway regulates the activities of RXRs. RXR 
      antagonists completely prevented and RXR agonists were more effective than RA in 
      inducing neuritogenesis. Thus, RXRs are in the final common path and may be 
      therapeutic targets to attenuate retinal remodeling and facilitate global 
      intervention methods in blinding diseases and other neurodegenerative disorders.
FAU - Lin, Yanhua
AU  - Lin Y
AD  - Department of Ophthalmology, John A. Moran Eye Center, University of Utah, Salt 
      Lake City, UT, USA.
FAU - Jones, Bryan W
AU  - Jones BW
FAU - Liu, Aihua
AU  - Liu A
FAU - Tucker, James F
AU  - Tucker JF
FAU - Rapp, Kevin
AU  - Rapp K
FAU - Luo, Ling
AU  - Luo L
FAU - Baehr, Wolfgang
AU  - Baehr W
FAU - Bernstein, Paul S
AU  - Bernstein PS
FAU - Watt, Carl B
AU  - Watt CB
FAU - Yang, Jia-Hui
AU  - Yang JH
FAU - Shaw, Marguerite V
AU  - Shaw MV
FAU - Marc, Robert E
AU  - Marc RE
LA  - eng
GR  - EY014800/EY/NEI NIH HHS/United States
GR  - EY08123/EY/NEI NIH HHS/United States
GR  - EY015128/EY/NEI NIH HHS/United States
GR  - R01 EY019298/EY/NEI NIH HHS/United States
GR  - R01 EY015128/EY/NEI NIH HHS/United States
GR  - EY002576/EY/NEI NIH HHS/United States
GR  - R01 EY002576/EY/NEI NIH HHS/United States
GR  - EY019298/EY/NEI NIH HHS/United States
GR  - R01 EY008123/EY/NEI NIH HHS/United States
GR  - P30 EY014800/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 - 20110922
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Rara protein, mouse)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (retinoic acid receptor beta)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.105 (retinol dehydrogenase)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - P6W5IXV8V9 (glutamate receptor ionotropic, AMPA 2)
SB  - IM
MH  - Alcohol Oxidoreductases/genetics
MH  - Alitretinoin
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
MH  - Disease Models, Animal
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Mutant Strains
MH  - Neurodegenerative Diseases/metabolism/pathology
MH  - Primary Cell Culture
MH  - Receptors, AMPA/metabolism
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Retinal Cone Photoreceptor Cells/metabolism/pathology
MH  - Retinal Degeneration/*metabolism/*pathology
MH  - Retinal Rod Photoreceptor Cells/metabolism/pathology
MH  - Retinoic Acid Receptor alpha
MH  - Signal Transduction/physiology
MH  - Tretinoin/metabolism
MH  - Vision, Ocular/*physiology
MH  - Retinoic Acid Receptor gamma
PMC - PMC3250249
EDAT- 2011/09/24 06:00
MHDA- 2012/03/01 06:00
PMCR- 2013/01/01
CRDT- 2011/09/24 06:00
PHST- 2011/09/24 06:00 [entrez]
PHST- 2011/09/24 06:00 [pubmed]
PHST- 2012/03/01 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - fj.11-192914 [pii]
AID - 11-192914 [pii]
AID - 10.1096/fj.11-192914 [doi]
PST - ppublish
SO  - FASEB J. 2012 Jan;26(1):81-92. doi: 10.1096/fj.11-192914. Epub 2011 Sep 22.