Ciliary neurotrophic factor induces glial fibrillary acidic protein in retinal Müller cells through the JAK/STAT signal transduction pathway

Ying Wang, Sylvia B Smith, Judy Mosinger Ogilvie, Doris J. McCool, Vijay Sarthy

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Purpose. 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.

Original languageEnglish (US)
Pages (from-to)305-312
Number of pages8
JournalCurrent Eye Research
Volume24
Issue number4
DOIs
StatePublished - Oct 23 2002

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Ciliary Neurotrophic Factor
Glial Fibrillary Acidic Protein
Signal Transduction
Immunohistochemistry
Intravitreal Injections
Immunoblotting
Phosphotransferases
Cell Line

Keywords

  • Cytokine
  • Gliosis
  • Müller cell
  • Retina
  • Signal transduction

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Ciliary neurotrophic factor induces glial fibrillary acidic protein in retinal Müller cells through the JAK/STAT signal transduction pathway. / Wang, Ying; Smith, Sylvia B; Ogilvie, Judy Mosinger; McCool, Doris J.; Sarthy, Vijay.

In: Current Eye Research, Vol. 24, No. 4, 23.10.2002, p. 305-312.

Research output: Contribution to journalArticle

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abstract = "Purpose. Intravitreal injection of ciliary neurotrophic factor (CNTF) is known to induce glial intermediate filament protein (GFAP) expression in retinal M{\"u}ller cells. Because CNTF binding can activate multiple signaling kinases, we have examined the involvement of JAK/STAT pathway in GFAP induction in M{\"u}ller 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 M{\"u}ller cell line, rMC-1. Results. In protein extracts of CNTF-injected eyes, retinal explants and the M{\"u}ller 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 M{\"u}ller cells through the JAK/STAT signaling pathway.",
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AU - Sarthy, Vijay

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