Endothelial TGFβ signaling regulates choroidal neovascularization severity via myeloid–endothelial interaction

The blood-retinal barrier (BRB) is essential for maintaining retinal homeostasis, yet its disruption contributes to pathological angiogenesis in diseases such as neovascular age-related macular degeneration (nAMD). Here, we investigated how endothelial TGF-β signaling interacts with microglia to regulate choroidal neovascularization (CNV). Using a laser-induced CNV model in mice with endothelial-specific Tgfbr2 deletion (Tgfbr2∆EC) and concomitant microglia depletion via PLX5622, we demonstrate that loss of endothelial TGF-β signaling significantly exacerbates CNV, an effect fully rescued by microglia depletion. Bulk RNA sequencing and RNAscope analyses of CNV lesions identified fibrinogen alpha chain (Fga) as a microglia-derived factor upregulated exclusively in Tgfbr2∆EC mice. These findings suggest a TGF-β-dependent interaction between endothelial cells and microglia that promotes angiogenesis through microglia derived Fga expression.