MicroRNA-28 potentially regulates the photoreceptor lineage commitment of Müller glia-derived progenitors

Abstract

Retinal degenerative diseases ultimately result into irreversible photoreceptor death or loss. At present, the most promising treatment for these diseases is cell replacement therapy. Müller glia are the major glia in the retina, displaying cardinal features of retinal progenitor cells, and can be candidate of seed cells for retinal degenerative diseases. Here, mouse retinal Müller glia dissociated and cultured in vitro amplified and were dedifferentiated into Müller glia-derived progenitors (MGDPs), demonstrating expression of stem/progenitor cell markers Nestin, Sox2 and self-renewal capacity. MicroRNAs (miRNAs) play unique roles in the retinogenesis, so we hypothesized miRNAs would contribute to photoreceptor lineage commitment of MGDPs. By TargetScan, Miranda, and Pictar bioinformatics, gain/loss-of-function models, dual luciferase assay, we identified and validated that miR-28 targeted the photoreceptor-specific CRX transcription factor. Anti-miR-28 could induce MGDPs to differentiate into neurons strongly expressing CRX and Rhodopsin, while miR-28 mimic suppressed CRX and Rhodopsin expression. Knockdown of CRX by siRNA blocked the expression of CRX and Rhodospin upregulated by anti-miR-28, indicating that anti-miR-28 potentially induced photoreceptor commitment of MGDPs by targeting CRX, but more experiments are necessary to confirm their role in differentiation.

Temporal Requirement ofMab21l2During Eye Development in Chick Reveals Stage-Dependent Functions for Retinogenesis

“…Previous studies have suggested that micro (mi)RNAs regulate the temporal order of retinogenesis by inhibiting transcription factors required for RPC differentiation. 38,39 Similar to our findings, these miRNAs appear to promote differentiation downstream of the cell cycle setting. 38 Interestingly, it has been shown that Mab21l2 protein binds to single-stranded (ss)RNA, but not ssDNA, 8 implying that Mab21l2 might bind to miRNA.…”

Photoreceptor protection by mesenchymal stem cell transplantation identifies exosomal MiR-21 as a therapeutic for retinal degeneration

“…Especially, exosomal transfer of microRNAs has been extensively reported to mediate effects of MSCT in treating a range of disorders [24][25][26]. In this regard, studies have identified individual microRNAs that play important roles in regulating ocular and retinal cell function, including those essential for photoreceptor maturation, maintenance, and visual function [27][28][29]. Furthermore, microRNA dysregulation has been revealed to be associated with photoreceptor death in the degenerating retina [30,31].…”

Emerging roles of non‐coding RNAs in retinal diseases: A review

“…miR‐181a/b was found to regulate retinal axon specification and growth in establishing the visual system 60 . miR‐28 was reported to induce photoreceptor lineage commitment of Müller glia‐derived progenitors (MGDPs) by targeting CRX 61 . miR‐24a was shown to regulate the development of the neural retina in Xenopus by repressing the proapoptotic factors caspase 9 and apaf1 62 .…”