Non-mammalian vertebrates such as fish and birds respond to injury to the retina by de-differentiation of Müller Glia (MG), which can proliferate and then re-differentiate down a neuronal lineage to restore lost neurons. Mammals, however, do not have this capacity, so their response to retinal injury is limited. There is therefore significant interest in identifying factors that, when expressed, could be manipulated to trigger neurogenic activity in MG. Stefanie Wohl and colleagues have previously shown that overexpression of the microRNAs miR-124, miR-9 and miR-9* can promote reprogramming. Now, they undertake a more global analysis of the miRNA profile of MG and retinal progenitor cells (RPCs), identifying other miRNAs that can influence neurogenic activity of MG in culture. They find that overexpression of miR-25 and inhibition of let-7 in MG promotes an RPC-like identity, with the manipulated cells then showing enhanced neurogenic potential. The authors show that the transcription factors Ascl1 and Klf4, as well as members of the Rest complex, are regulated by these miRNAs and may be important in determining the neurogenic potential of MG. Although the effects of these miRNAs in the retina in vivo or under injury conditions have yet to be explored, this work provides new insights into the mechanisms regulating reprogramming and regeneration in the mammalian retina.
