Fig. 8.

Suggested mechanism for microRNA regulation of Müller glia state. miRNA depletion in retinas and cultures of MG in the Dicer-CKO_MG mice leads to disorganization of the normal retinal architecture due to MG migration and aggregation, in vivo and in vitro. The gene upregulated the most in the Dicer-CKO_MG and responsible for MG migration and aggregation is Bcan, which encodes for the chondroitin sulfate proteoglycan Brevican. AAV-mediated overexpression of Brevican in wild-type MG also leads to MG migration and aggregation while blocking antibodies to Brevican prevent MG aggregation in dissociated MG cultures from Dicer-CKO_MG retinas. miR-9, one of the most highly expressed miRNAs in MG (mGliomiRs), targets the 3′UTR of Brevican and miR-9 mimics treatment of Dicer-CKO_MG MG can prevent MG aggregation and restore normal MG shape in vitro