gp130 activation in Müller cells is not essential for photoreceptor protection from light damage.
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.
Ueki
Yumi
Y
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Chollangi
Srinivas
S
Le
Yun-Zheng
YZ
Ash
John D
JD
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects / Q000528:radiation effects*; D004596:Electroretinography; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D055254:Night Vision / Q000187:drug effects / Q000528:radiation effects; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects*; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D050796:STAT3 Transcription Factor / Q000378:metabolism
D053605:Leukemia Inhibitory Factor; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D050822:Cytokine Receptor gp130