Yin Zhiyuan, Kang Jiahui, Cheng Xuan, Gao Hui, Huo Shujia, Xu Haiwei
Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Neural Regen Res. 2025 Apr 1;20(4):946-959. doi: 10.4103/NRR.NRR-D-23-01612. Epub 2024 Apr 16.
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.
缪勒胶质细胞作为视网膜内突出的神经胶质细胞，在维持健康和患病状态下的视网膜内环境稳定方面发挥着重要作用。在斑马鱼等低等脊椎动物中，这些细胞负责视网膜的自发再生，即内源性缪勒胶质细胞进行增殖，转化为缪勒胶质细胞衍生的祖细胞，随后再生出功能恢复的整个视网膜。相反，小鼠和人类视网膜中的缪勒胶质细胞表现出有限的神经重编程能力。因此，缪勒胶质细胞重编程是治疗神经退行性眼部疾病的一种有前景的策略。通过各种技术，小鼠中的缪勒胶质细胞重编程已取得显著成功。分子、遗传、表观遗传、形态学和生理学评估的进展使得记录和研究小鼠中的缪勒胶质细胞编程过程变得更加容易。然而，仍然存在阻碍提高重编程效率和成熟度的问题。因此，了解重编程机制对于探索提高缪勒胶质细胞重编程效率的因素以及开发新的缪勒胶质细胞重编程策略至关重要。本综述描述了相对成功的缪勒胶质细胞重编程策略的最新进展。它还为在小鼠中开发新的缪勒胶质细胞重编程策略提供了基础，包括表观遗传重塑、代谢调节、免疫调节、化学小分子调节、细胞外基质重塑和细胞 - 细胞融合，以实现小鼠中的缪勒胶质细胞重编程。
