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.
Highlights
To better understand the roles of microRNAs in glial function, we used a conditional deletion of Dicer[1] (Dicer-CKOMG) in retinal Müller glia (MG)
We focused on Brevican for further analysis, since this protein has been implicated in astrocyte proliferation and migration and might be involved in the MG migration that occurs after Dicer[1] deletion
We generated a conditional deletion of Dicer[1] to determine the role of miRNAs in MG cells (Fig. 8). (1) We found that miRNA depletion in MG leads to disorganization of the normal retinal architecture due to MG migration and aggregation
Summary
To better understand the roles of microRNAs in glial function, we used a conditional deletion of Dicer[1] (Dicer-CKOMG) in retinal Müller glia (MG). By 6 months after Dicer[1] deletion, the MG form large aggregations and severely disrupt normal retinal architecture and function. The loss of Dicer[1] in MG results in a decline of all the miRNAs that are normally highly expressed in these cells, and RNA-Seq shows that the gene with the greatest increase in the Dicer-CKOMG is Bcan (encoding Brevican), a chondroitin sulfate proteoglycan[29, 30]. Our results show that miRNAs are required in MG for the maintenance of retinal structure and function
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
