Ablation Of Mature Mir-183 Leads To Retinal Dysfunction In Mice

PURPOSE. The microRNA cluster miR-183C, which includes miR-183 and two other genes, is critical for multiple sensory systems. In mouse retina, removal of this cluster results in photoreceptor defects in polarization, phototransduction, and outer segment elongation. However, the individual roles of the three components of this cluster are not clearly known. We studied the separate role of mouse miR-183 in in vivo.METHODS. miR-183 knockout mice were generated using the CRISPR/Cas9 genome-editing system. Electroretinography were carried out to investigate the changes of retinal structures and function. miR-183 was overexpressed by subretinal adeno-associated virus (AAV) injection in vivo. Rnf217, a target of miR-183 was overexpressed by cell transfection of the photoreceptor-derived cell line 661W in vitro. RNA sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to compare the gene expression changes in AAV-injected mice and transfected cells.RESULTS. The miR-183 knockout mice showed progressively attenuated electroretinogram responses. Over- or under-expression of Rnf217, a direct target of miR-183, misregulated expression of cilia-related BBSome genes. Rnf217 overexpression also led to compromised electroretinography responses in WT mice, indicating that it may contribute to functional abnormalities in miR-183 knockout mice.CONCLUSIONS. miR-183 is essential for mouse retinal function mediated directly and indirectly through Rnf217 and cilia-related genes. Our findings provide valuable insights into the explanation and analysis of the regulatory role of the individual miR-183 in miR-183C.