Targeting the neurovascular unit in retinal fibrosis: mechanisms and therapeutic perspectives

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.