The Angiofibrotic Switch in Retinal and Choroidal Vascular Diseases: Mechanistic Drivers of Angiogenesis and Endothelial-Mesenchymal Transition.

The angiofibrotic switch refers to the pathologic transition from active angiogenesis to fibrosis, a process that contributes to disease progression in retinal and choroidal neovascular diseases, such as age-related macular degeneration and proliferative diabetic retinopathy. This switch marks the replacement of newly formed, fragile blood vessels with fibrotic tissue, ultimately leading to scarring and permanent vision loss. Understanding this process is crucial, as fibrosis results in severe visual impairment and, currently, no anti-fibrotic therapies exist. Central to the angiofibrotic switch is endothelial-mesenchymal transition, a process where endothelial cells lose their vascular endothelial identity and acquire mesenchymal properties, contributing to extracellular matrix deposition and fibrosis. This review explores the cellular and molecular mechanisms underlying the angiofibrotic switch, emphasizing the interplay between angiogenesis, endothelial-mesenchymal transition, and metabolic dysregulation in driving fibrosis. Key mediators, such as transforming growth factor-β and vascular endothelial growth factor, are discussed in the context of their dual roles in promoting angiogenesis and fibrosis. This review underlines the need for early detection methods and targeted therapies to mitigate the angiofibrotic switch and improve outcomes in patients with neovascular retinal and choroidal diseases. By unraveling the complexities of this transition, this review aims to provide a framework for developing innovative diagnostic and therapeutic strategies to prevent fibrosis and mitigate vision loss in retinal and choroidal neovascular diseases.