Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

Müller glia, as prominent glial cells within the retina, plays a significant role in maintaining retinal homeostasis in both healthy and diseased states. In lower vertebrates like zebrafish, these cells assume responsibility for spontaneous retinal regeneration, wherein endogenous Müller glia undergo proliferation, transform into Müller glia-derived progenitor cells, and subsequently regenerate the entire retina with restored functionality. Conversely, Müller glia in the mouse and human retina exhibit limited neural reprogramming. Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders. Müller glia reprogramming in mice has been accomplished with remarkable success, through various technologies. Advancements in molecular, genetic, epigenetic, morphological, and physiological evaluations have made it easier to document and investigate the Müller glia programming process in mice. Nevertheless, there remain issues that hinder improving reprogramming efficiency and maturity. Thus, understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency, and for developing novel Müller glia reprogramming strategies. This review describes recent progress in relatively successful Müller glia reprogramming strategies. It also provides a basis for developing new Müller glia reprogramming strategies in mice, including epigenetic remodeling, metabolic modulation, immune regulation, chemical small-molecules regulation, extracellular matrix remodeling, and cell-cell fusion, to achieve Müller glia reprogramming in mice.