Document Detail


gp130 activation in Müller cells is not essential for photoreceptor protection from light damage.
MedLine Citation:
PMID:  20238070     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Members of IL-6 family cytokines, such as leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF), activate the common signal-transducing receptor gp130. We and others have previously shown that application of exogenous gp130 ligands promotes photoreceptor survival in light-induced and inherited retinal degeneration in animal models. While there is strong evidence that gp130 plays an essential role in photoreceptor protection, it is not clear whether protection is cell-autonomous in photoreceptors or an effect of Müller cell activation. To investigate the role of Müller cells in gp130-mediated photoreceptor protection, we have generated conditional gp130 knockout (KO) mice in retinal Müller cells using the Cre/lox system. Western blot and immunohistochemical analyses show that in our conditional gp130 KO mice, approximately 50% Müller cells no longer respond to LIF with activation of known downstream signaling proteins, STAT3 and ERK1/2. Despite the loss of gp130 activity in many Müller cells, intravitreal injection of LIF still induced significant degree of photoreceptor protection that was comparable to normal littermates. These data suggest that Müller cell activation of gp130 is not essential for photoreceptor protection, and support the hypothesis that the protection is mediated by cell-autonomous mechanisms in photoreceptors.
Authors:
Yumi Ueki; Srinivas Chollangi; Yun-Zheng Le; John D Ash
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Advances in experimental medicine and biology     Volume:  664     ISSN:  0065-2598     ISO Abbreviation:  Adv. Exp. Med. Biol.     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-18     Completed Date:  2011-09-12     Revised Date:  2013-12-13    
Medline Journal Info:
Nlm Unique ID:  0121103     Medline TA:  Adv Exp Med Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  655-61     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Death / drug effects,  radiation effects
Cytokine Receptor gp130 / metabolism*
Cytoprotection / drug effects,  radiation effects*
Electroretinography
Leukemia Inhibitory Factor / pharmacology
Light*
Mice
Mice, Knockout
Night Vision / drug effects,  radiation effects
Photoreceptor Cells, Vertebrate / drug effects,  pathology*,  radiation effects*
Protein Transport / drug effects,  radiation effects
STAT3 Transcription Factor / metabolism
Grant Support
ID/Acronym/Agency:
P20 RR017703/RR/NCRR NIH HHS; P30 EY012190/EY/NEI NIH HHS; R01 EY016459/EY/NEI NIH HHS; R01 EY016459/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Leukemia Inhibitory Factor; 0/STAT3 Transcription Factor; 0/Stat3 protein, mouse; 133483-10-0/Cytokine Receptor gp130

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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