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S. Reichman, R. Kiran Reddy, S. Lambard, A. Lardenois, O. Poch, D. Zack, J. Sahel, T. Léveillard; The Homeobox Genes CRX, CHX10 and VSX1 Regulate RdCVF Promoter Activity in Bipolar Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2191. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The identification of Rod derived viability factor (RdCVF), by cloning expression, which promotes cone photoreceptor viability, offers new treatment possibilities for retinitis pigmentosa. Here we aimed to identify transcription factors (TFs), which are able to regulate the RdCVF promoter.
Four steps were used to identify TFs able to bind and activate the RdCVF promoter. 1. Bioinformatic analysis: to predict TF binding elements of a 5’ up-stream sequence of 4.2kb in size. 2. Transcriptomic analysis: to indentify TFs expressed in photoreceptors (Affymetrix). 3. Clone extraction from EST library: TFs selected, after cross reference of Bioinformatic and transcriptomic analysis, were extracted from a retinal library sequenced at the French National Center for Sequencing (Genoscope). 4. Test of the TFs: by transient transfection in HEK 293 cells with dual luciferase assays. Investigation of the profile of RdCVF expression in wild type and RdCVF knock-out mice by in situ hybridization and immunostaning.
Twenty-eight TFs were tested and three homeobox genes CRX, CHX10 and VSX1 were found to be able to transactivate the RdCVF promoter in a dose dependant manner. These homeobox genes are known for their role in regulating development and differentiation of photoreceptor (CRX) and bipolar cells (CHX10 and VSX1). Furthermore, there is a synergetic activity between CHX10 and VSX1. Our in situ hybridization studies showed low level of RdCVF transcript in the inner nuclear layer, likely corresponding to bipolar cells.
This finding suggests potential therapeutic treatment for retinitis pigmentosa by increasing RdCVF expression by cells, such as bipolar cells, which are close to the degenerating photoreceptors.
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