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 the Crb1 gene, 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.

Adherens junction, Disease model, Genetics, Microcirculation, Retinal blood vessels, Retinal degeneration
dx.doi.org/10.1523/JNEUROSCI.3412-14.2015, hdl.handle.net/1765/82425
The Journal of Neuroscience
Erasmus Center for Biomics

Zhao, M, Andrieu-Soler, C, Kowalczuk, L, Cortés, M.P, Berdugo, M, Dernigoghossian, M, … Behar-Cohen, F. (2015). A new CRB1 rat mutation links Müller glial cells to retinal telangiectasia. The Journal of Neuroscience, 35(15), 6093–6106. doi:10.1523/JNEUROSCI.3412-14.2015