A New CRB1 Rat Mutation Links Muller Glial Cells to Retinal Telangiectasia

M Zhao, C Andrieu-Soler, L Kowalczuk, MP Cortes, M Berdugo, M Dernigoghossian, F Halili, JC Jeanny, B Goldenberg, M Savoldelli, M El Sanharawi, MC Naud, Wilfred van Ijcken, R Pescini-Gobert, D Martinet, A Maass, J Wijnholds, P Crisanti, C Rivolta, F Behar-Cohen

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We have identified and characterized a spontaneous Brown Norway from Janvier rat strain (BN-J) presenting a progressive retinal degeneration associated with early retinal telangiectasia, neuronal alterations, and loss of retinal Muller glial cells resembling human macular telangiectasia type 2 (MacTel 2), which is a retinal disease of unknown cause. Genetic analyses showed that the BN-J phenotype results from an autosomal recessive indel novel mutation in the Crb1 gene, causing dislocalization of the protein from the retinal Muller glia (RMG)/photoreceptor cell junction. The transcriptomic analyses of primary RMG cultures allowed identification of the dysregulated pathways in BN-J rats compared with wild-type BN rats. Among those pathways, TGF-beta and Kit Receptor Signaling, MAPK Cascade, Growth Factors and Inflammatory Pathways, G-Protein Signaling Pathways, Regulation of Actin Cytoskeleton, and Cardiovascular Signaling were found. Potential molecular targets linking RMG/photoreceptor interaction with the development of retinal telangiectasia are identified. This model can help us to better understand the physiopathologic mechanisms of MacTel 2 and other retinal diseases associated with telangiectasia.
Original languageUndefined/Unknown
Pages (from-to)6093-6106
Number of pages14
JournalJournal of Neuroscience
Issue number15
Publication statusPublished - 2015

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