Endothelial TGFβ signaling modulates choroidal neovascularization severity via myeloid-endothelial cell interaction.

INTRODUCTION

The blood-retinal barrier (BRB) is essential for maintaining retinal homeostasis, consequently its disruption contributes to pathological angiogenesis in diseases such as neovascular age-related macular degeneration (nAMD). Choroidal neovascularization (CNV) is considered as a hallmark of nAMD. These newly formed vessels break through the BRB leading to rapid and severe vision loss. Here, we investigated how endothelial TGFβ signaling interacts with mononuclear phagocytes (MP), such as microglia to regulate choroidal neovascularization (CNV).

METHODS

In this study, we used a laser-induced CNV model in mice with endothelial-specific Tgfbr2 deletion and concomitant MP depletion via PLX5622.

RESULTS

We demonstrate that loss of endothelial TGFβ signaling significantly exacerbates CNV. Strikingly, this effect is fully rescued by MP depletion. Transcriptome and RNA localization of CNV lesions identified fibrinogen alpha chain (Fga) as a MP-derived factor that is exclusively upregulated in mice without endothelial TGFβ signaling.

DISCUSSION: These findings suggest a novel TGFβ-dependent interaction between endothelial cells and MP that promotes angiogenesis through microglia derived Fga expression.