Ciliary neurotrophic factor induces glial fibrillary acidic protein in retinal Müller cells through the JAK/STAT signal transduction pathway.
OBJECTIVE
Intravitreal injection of ciliary neurotrophic factor (CNTF) is known to induce glial intermediate filament protein (GFAP) expression in retinal Müller cells. Because CNTF binding can activate multiple signaling kinases, we have examined the involvement of JAK/STAT pathway in GFAP induction in Müller cells.


METHODS
CNTF was injected intravitreally into mouse eyes. Immunocytochemistry and immunoblotting were used to study GFAP and STAT3-p (phosphorylated STAT3) levels either in mouse eyes, retinal explant cultures or in a Müller cell line, rMC-1.


RESULTS
In protein extracts of CNTF-injected eyes, retinal explants and the Müller cells, there was a substantial increase in STAT3-p level. Immunocytochemistry showed that STAT3-p was now present in many cell bodies in the INL and the GCL. To prove that CNTF acted via the JAK-STAT pathway, rMC-1 cells were transfected with a dominant-negative STAT3 mutant prior to treatment with CNTF. In the immunoblots of transfected cells, there was decrease in GFAP level.


CONCLUSIONS
The results establish that CNTF can induce GFAP expression in retinal Müller cells through the JAK/STAT signaling pathway.
D000818:Animals; D002460:Cell Line; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D005123:Eye / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D012160:Retina / Q000166:cytology* / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D014018:Tissue Distribution; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology
D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators