Work

Single-cell and spatial analyses reveal endothelial–macrophage inflammatory crosstalk in dry age-related macular degeneration

Year: 2026

Type: article

Abstract: BACKGROUND: Dry age-related macular degeneration (AMD) is characterized by progressive degeneration of the retinal pigment epithelium-choroid interface, accompanied by immune dysregulation. However, the cellular interactions and regulatory mechanisms driving macrophage activation in this process remain incompletely understood. METHODS: We integrated spatial transcriptomics and single-cell RNA sequencing data from a photo-oxidative damage mouse model and human dry AMD samples. A series of bioinformatic analyses, including cell-cell communication analysis, enrichment analysis, and pseudotime trajectory analysis, were performed to characterize cellular features and regulatory pathways. RESULTS: In the photo-oxidative damage mouse model, the RPE-choroid region showed marked infiltration of myeloid cells. In human dry AMD samples, SLC16A10-positive macrophages were enriched and exhibited pro-inflammatory features. Further analysis revealed that endothelial cells regulate SLC16A10-positive macrophages through the TNFSF10-TNFRSF10B pathway, with NFKB1 acting as a key regulator to activate NF-κB signaling, thereby promoting the formation of a vascular-immune inflammatory niche. CONCLUSIONS: This study systematically characterizes immune remodeling in the RPE-choroid region in dry AMD and identifies an endothelial-macrophage TNFSF10-TNFRSF10B-NF-κB signaling pathway that drives disease progression. These findings provide new insights into disease mechanisms and suggest potential therapeutic targets for dry AMD.

Source: Journal of Translational Medicine

DOI: 10.1186/s12967-026-08393-7