Müller glial microRNAs are required for the maintenance of glial homeostasis and retinal architecture

Stefanie G. Wohl, Nikolas L. Jorstad, Edward M. Levine and Thomas A. Reh ()
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Stefanie G. Wohl: University of Washington, Health Sciences Center
Nikolas L. Jorstad: University of Washington, Health Sciences Center
Edward M. Levine: Vanderbilt University
Thomas A. Reh: University of Washington, Health Sciences Center

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: Abstract To better understand the roles of microRNAs in glial function, we used a conditional deletion of Dicer1 (Dicer-CKOMG) in retinal Müller glia (MG). Dicer1 deletion from the MG leads to an abnormal migration of the cells as early as 1 month after the deletion. By 6 months after Dicer1 deletion, the MG form large aggregations and severely disrupt normal retinal architecture and function. The most highly upregulated gene in the Dicer-CKOMG MG is the proteoglycan Brevican (Bcan) and overexpression of Bcan results in similar aggregations of the MG in wild-type retina. One potential microRNA that regulates Bcan is miR-9, and overexpression of miR-9 can partly rescue the effects of Dicer1 deletion on the MG phenotype. We also find that MG from retinitis pigmentosa patients display an increase in Brevican immunoreactivity at sites of MG aggregation, linking the retinal remodeling that occurs in chronic disease with microRNAs.

Date: 2017
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DOI: 10.1038/s41467-017-01624-y

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