Expression of cytokine signal transduction components in the postnatal mouse retina.
OBJECTIVE
Members of the ciliary neurotrophic factor (CNTF) family of cytokines have been shown to influence neuronal differentiation during retinal development and enhance cell survival in various retinal degeneration models. However, the cellular mechanism of CNTF signaling and the target cell types for CNTF in the developing retina remain unidentified. The purpose of this study is to characterize expression patterns of proteins involved in cytokine signal transduction in the mouse retina, thus to assess the potential responsiveness of different retinal cell types to CNTF-like cytokine signals.


METHODS
The expression profiles of various cytokine signal transduction components, including receptor subunits CNTF receptor alpha (CNTFRa) and gp130, intracellular protein kinases, Jak2 and Tyk2, as well as latent transcription factors, STAT1 and STAT3, were determined by immunohistochemical staining of mouse retinal sections derived from different postnatal stages. In addition, the distribution of ERK was studied by immunofluorescent staining.


RESULTS
In the neonatal retina, intense staining signals for gp130, CNTFRalpha, Jak2, Tyk2, STAT1, and STAT3 were present in the differentiated ganglion cell layer and the developing inner plexiform layer of the mouse retina. Detectable staining signals were also observed in the ventricular zone of the early postnatal mouse retina. From P5 to P10, cytokine signaling molecules also accumulated in the developing outer plexiform layer. In the adult retina, cytokine signaling components examined were localized to the ganglion cell layer, the inner nuclear layer, and the two plexiform layers. In addition, regions corresponding to the inner and/or outer segments of the photoreceptor cells showed positive staining for cytokine signaling components. In contrast, the ERK2 protein kinase was found throughout the neonatal retina. In the mature retina, ERK2 was concentrated in the ganglion cells and the inner plexiform layer, while a lesser expression of ERK2 was detected in the inner nuclear layer, the outer plexiform layers, and the outer nuclear layer.


CONCLUSIONS
In the neonatal mouse retina, signaling components of the Jak-STAT pathway and ERK2 are differentially expressed. All cytokine signaling components included in this study are expressed in the differentiated inner retina as well as in cells occupying the ventricular zone, suggesting that both postmitotic neurons and proliferative progenitors may directly respond to CNTF-like cytokines during postnatal development. The distribution of cytokine signaling pathway components in the adult mouse retina is consistent with previous findings that ganglion cells and Müller glia are the primary target cell types for CNTF.
Rhee
Kun Do
KD
Department of Ophthalmology, Jules Stein Eye Institute, David Geffen School of Medicine, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
Yang
Xian-Jie
XJ
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005136:Eye Proteins / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D007124:Immunoenzyme Techniques; D053614:Janus Kinase 2; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D020801:Receptor, Ciliary Neurotrophic Factor / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015398:Signal Transduction; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D004268:DNA-Binding Proteins; D005136:Eye Proteins; C494200:Il6st protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020801:Receptor, Ciliary Neurotrophic Factor; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C499356:Tyk2 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1