Age-related macular degeneration is the leading cause of irreversible blindness in the elderly.Subretinal fibrosis secondary to neovascular age-related macular degeneration is an important factor in irreversible vision loss. Due to the lack of fibroblasts in retinal tissue, mesenchymal transformation becomes the main cellular source of subretinal fibrosis. During this process, multiple cell types, including retinal pigment epithelial cells, vascular endothelial cells, macrophages, and perivascular cells are driven by key cytokines such as transforming growth factor-beta (TGF-β) and a chronic inflammatory microenvironment to transdifferentiate into myofibroblasts through epithelial–mesenchymal transition and endothelial–mesenchymal transition. Together, these cells constitute the cellular basis of fibrosis. In addition, Müller cells and fibroblasts derived from the peripheral circulation also contribute to this process. Future preventive and therapeutic strategies should therefore simultaneously target both fibrotic and inflammatory pathways. At present, experimental studies have demonstrated the potential of interventions targeting TGF-β, platelet-derived growth factor, and Yes-associated protein signaling, as well as combined anti-inflammatory strategies involving interleukin-6 and complement component 3a. Further elucidation of the underlying molecular mechanisms will facilitate the development of precision therapies and offer new hope for improving visual outcomes in affected patients.
