Targeting BMP4 as a therapeutic strategy for neovascularization and fibrosis in age-related macular degeneration

This study investigates the role of bone morphogenetic protein-4 (BMP4) in age-related macular degeneration (AMD), with a focus on its effects on subretinal fibrosis and choroidal neovascularization (CNV). Using a mouse model of laser-induced CNV, we found that BMP4 expression was significantly elevated in CNV lesions. BMP4 was shown to promote fibroblast proliferation and their differentiation into myofibroblasts, as indicated by increased expression of α-smooth muscle actin (α-SMA). Additionally, BMP4 promoted the transition of endothelial progenitor cells (EPCs) into endothelial cells (ECs), a process that was modulated by mitochondrial function. Intravitreal administration of Noggin, a BMP4 inhibitor, significantly reduced CNV lesion volume and decreased the expression of CD31 and α-SMA, suggesting a decrease in neovascularization and fibrosis. These findings underscore BMP4's critical role in AMD pathogenesis by driving both angiogenesis and fibrosis. Targeting BMP4 with Noggin presents a promising therapeutic approach for AMD, addressing both neovascularization and fibrosis in a single intervention, and highlights BMP4 as a potential novel target for AMD therapy.