1. A new CRB1 rat mutation links Müller glial cells to retinal telangiectasia
- Author
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Patricia Crisanti, Carlo Rivolta, Marilyn Dernigoghossian, Rosanna Pescini-Gobert, Charlotte Andrieu-Soler, Alejandro Maass, Jean-Claude Jeanny, Min Zhao, Laura Kowalczuk, Marie-Christine Naud, Michèle Savoldelli, Wilfred F. J. van IJcken, Danielle Martinet, Francisco Halili, Francine Behar-Cohen, Jan Wijnholds, María Paz Cortés, Mohamed El Sanharawi, Marianne Berdugo, Brigitte Goldenberg, Netherlands Institute for Neuroscience (NIN), and Cell biology
- Subjects
Retinal degeneration ,Neurons/ultrastructure ,Retinal Degeneration/genetics ,Telangiectasis/complications ,adherens junction ,Photoreceptor cell ,chemistry.chemical_compound ,Visual Pathways/pathology ,genetics ,Fluorescein Angiography ,Cells, Cultured ,Macular telangiectasia ,Neurons ,Genetics ,medicine.diagnostic_test ,General Neuroscience ,Age Factors ,Articles ,Glial Fibrillary Acidic Protein/metabolism ,Retinal Vessels/pathology ,Cell biology ,Platelet Endothelial Cell Adhesion Molecule-1 ,Retinal telangiectasia ,medicine.anatomical_structure ,Ependymoglial Cells/pathology ,Muller glia ,Retinal Degeneration/etiology ,Signal Transduction ,Antigens, CD31/metabolism ,Mutation/genetics ,Eye Proteins/metabolism ,Ependymoglial Cells ,microcirculation ,Visual Pathways/ultrastructure ,Biology ,Eye Proteins/genetics ,retinal blood vessels ,Rats, Mutant Strains ,SDG 3 - Good Health and Well-being ,Glial Fibrillary Acidic Protein ,Electroretinography ,medicine ,Animals ,Retinal Degeneration/pathology ,Visual Pathways ,Telangiectasis ,Eye Proteins ,Retinal Vessels/ultrastructure ,Telangiectasis/genetics ,Signal Transduction/physiology ,Neurons/pathology ,disease model ,Retinal Vessels ,Retinal ,medicine.disease ,Actin cytoskeleton ,Rats ,Disease Models, Animal ,Animals, Newborn ,nervous system ,chemistry ,Ependymoglial Cells/ultrastructure ,Mutation ,retinal degeneration ,Ependymoglial Cells/metabolism - Abstract
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 Müller 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 theCrb1gene, causing dislocalization of the protein from the retinal Müller 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-β 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.
- Published
- 2015
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