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S.S. M. Zhang, M.–G. Liu, S. Patil, X.–Y. Fu, C.J. Barnstable; A global view of gene expression during CNTF initiated inhibition of rod development . Invest. Ophthalmol. Vis. Sci. 2004;45(13):678.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Ciliary neurotrophic factor (CNTF) has been shown to protect many types of neuronal cells in response to stress. On the other hand, the transduction pathways activated by CNTF also regulate rod photoreceptor differentiation in chick and mammals. Experiments clearly showed that the rod marker opsin did not appear in the outer retina layer after CNTF treatment at stages in which opsin was highly expressed in the control tissues. We have taken a global view of gene expression to determine whether the effet of CNTF is on opsin expression or on the formation of rod photoreceptor cells. Methods:In this study we used retinal explant cultures and cDNA microarrays, to generate a gene expression profile comparison between CNTF treated and untreated retinas from embryonic day 16 (E16) to postnatal day 10 (PN10). Retinas were collected from C57Bl/6 mice in these studies. RNA samples were pooled from CNTF treated or control retina explants cultured for 1, 3, 5, 7, 10, 12, and 15 days from C57Bl/6 E16 retinas (corresponding to E17, E19, PN1, PN3, PN5, PN7, and PN10 in vivo). Results:At day 7 after CNTF treatment (PN3), a sample of 10 rod cell–type enriched genes was all decreased at least 2 fold by CNTF (log2 >=–1). More than half of the decreased genes have similar expression profile, later onset during retina development. Thus, in addition to opsin, a broader set of rod genes is inhibited by CNTF, indicating that rod photoreceptor differentiation is inhibited by CNTF. We also analyzed other groups of genes with higher or lower expression profiles at different stages after CNTF application. Conclusions:CNTF inhibits the formation of rod photoreceptor cells. The data generated from this study also provide useful information for the analysis of CNTF initiated signal transduction pathways mediating this inhibition. It shows that studies of global–wide gene expression by individual growth factors or cytokines can be carried out using retinal explant cultures.
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