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D.R. Graham, J.D. Ash; Leukemia Inhibitory Factor (LIF) Blocks the Transcriptional Program Required for Rod Photoreceptor Differentiation. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5309.
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Purpose: We have previously shown that transgenic expression of LIF blocks the development of photoreceptors. In the presence of LIF, photoreceptors do not synthesize outer segments, and do not express rhodopsin or most other proteins that are normally located in the outer segments. The goal of this study is to identify the mechanism(s) of suppression of key transcription factors including, NRL and Nr2e3 and how LIF may regulate NRL expression. Methods: We have adopted real–time PCR, immuo–fluorescence and in situ hybridizations to determine which transcription factors may control photoreceptor development. Results: Real–time PCR data has shown that in the presence of LIF, expression of rhodopsin is undetectable, while the expression of medium– and short–wavelength opsins are less than 3% of normal. We have also found that NRL and Nr2e3 are reduced at least 5–fold when compared to normal retinas. In situ hybridization analysis has shown that NRL expression is below the level of detection in transgenic mice. Unlike mice lacking NRL or Nr2e3 we did not observe an increase in S– cones. Conclusions: Our expression analysis demonstrates that LIF dramatically inhibits rod photoreceptor development by down regulating the expression of NRL and Nr2e3. Basic helix–loop–helix genes have been shown to be essential for the differentiation and survival of photoreceptors. Based on their function and developmental expression, we suspect that these genes may regulate NRL expression and may be potential mechanisms by which LIF may regulate NRL. This hypothesis is under investigation.
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