Jun Zhang, Jiaojiao Feng, Jike Song, Hongsheng Bi
Retinal fibrosis represents an important pathological feature of several vision-threatening ocular diseases, including advanced diabetic retinopathy and neovascular age-related macular degeneration. Its progression may be associated with reactive changes in Müller glial cells and their acquisition of mesenchymal-like phenotypes. As the predominant glial population in the retina, Müller glial cells play crucial physiological roles in maintaining retinal homeostasis. However, under pathological conditions, they can become reactive and acquire mesenchymal- or myofibroblast-like features through a process referred to as glial-mesenchymal transition (GMT), potentially contributing to fibrotic remodeling. This review systematically examines the molecular mechanisms associated with Müller cell GMT, including the regulatory involvement of the TGF-β and Notch signaling pathways, inflammatory mediators, and oxidative stress. It discusses the potential contribution of GMT to retinal fibrotic progression. Furthermore, this article synthesizes the potential pathological and therapeutic relevance of GMT in related ocular diseases and discusses experimental intervention strategies targeting Müller cell phenotypic remodeling. Understanding the regulatory network of Müller cell GMT may inform the development of future therapeutic approaches to prevent or attenuate retinal fibrosis.