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X. Yang, K. Rhee, O. Goureau, S. Chen; Ciliary Neurotrophic Factor (cntf) Differentially Activates the Jak-stat and the Erk Pathways in the Developing Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2824.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Ciliary neurotrophic factor (CNTF) exhibits multiple biological effects in the developing retina, including affecting differentiation of photoreceptor cells, promoting axonal growth of ganglion cells, and inducing the maturation of astrocytes in the optic nerve. In addition, CNTF promotes retinal cell survival in a variety of rodent retinal degeneration models. This report focuses on the signaling pathways activated by CNTF and the target cell types responsive to CNTF signals in the postnatal mouse retina. Methods: The distribution of the receptor components and the intracellular signaling molecules mediating CNTF signals was examined by immunohistochemistry. The activated signaling pathways and the activation kinetics were determined by using Western blot analyses. The retinal cell types responding to CNTF signals were identified by double immunofluorescent staining of activated signaling molecules and retinal cell type markers. The effects of cytokine treatment on retinal differentiation were analyzed using cell type markers and signaling pathways inhibitors in retinal monolayer and explant cultures. Results: In the early postnatal retina, CNTF can activate both the JAK-STAT and the ERK signaling pathways. The response of the retinal cells is rapid and transient, correlating to the induction of inhibitors for cytokine signaling. The CNTF receptors and intracellular signaling components are distributed in both proliferating progenitor cells and postmitotic cells. CNTF differentially activates the STAT transcription factors and the ERK kinase among progenitors and postmitotic cells. CNTF promotes Muller glial cell differentiation and inhibits rod photoreceptor differentiation mainly through the JAK-STAT signaling pathway. Conclusions: CNTF signals through both the Jak-STAT and the ERK pathways in the developing mouse retina. However, these two pathways are differentially activated between progenitor cells and postmitotic cells, and play distinct roles in cell proliferation and differentiation.
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