REVIEW article
Front. Med.
Sec. Ophthalmology
Targeting the Neurovascular Unit in Retinal Fibrosis: Mechanisms and Therapeutic Perspectives
Wenyang Xu
Jie Zhang
Yanyu Shangguan
Ruoning Luo
Yanming Zhu
Yanlong Bi
Bing Li
Tongji Hospital Affiliated to Tongji University, Shanghai, China
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Abstract
Retinal fibrosis, a severe complication observed in conditions like age-related macular degeneration and diabetic retinopathy, characterized by aberrant myofibroblast activation and excessive extracellular matrix (ECM) deposition, which ultimately led to irreversible visual impairment. Currently, the mechanisms underlying retinal fibrosis remain unclear and existing treatments remain incompletely understood. Thus, a comprehensive understanding of disease mechanisms, together with the development of innovative therapeutic approaches, is essential for advancing effective treatment strategies. This review systematically examines the pathogenesis of retinal fibrosis from the perspective of the neurovascular unit (NVU), with a particular focus on the roles of endothelial cells, pericytes, and glial cells in fibrotic processes. It highlights key fibrotic mechanisms, including epithelial mesenchymal transition (EMT) as well as macrophage and pericyte-to-myofibroblast transitions (MMT/PMT). It further analyzes the molecular mechanisms that regulate myofibroblast activation and extracellular matrix deposition. Additionally, this review outlines potential therapeutic targets for the treatment of retinal fibrosis.
Summary
Keywords
Epithelial-MesenchymalTransition (EMT), Jagged/Notchsignaling pathway, myofibroblast, Neurovascular unit (NVU), Retinal fibrosis, TGF-β signaling pathway, therapeutic targets
Received
28 December 2025
Accepted
20 February 2026
Copyright
© 2026 Xu, Zhang, Shangguan, Luo, Zhu, Bi and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Yanlong Bi; Bing Li
Disclaimer
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