Journal Article

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

Chen, Yujie, Huang, Yimin, Hu, Yishan, Wang, Pan, Chen, Lin, Liu, Chuling, Chen, Jinghan, Pan, Guiping, Zhang, Yuxi, Wang, Yan

2026

Overview

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.

• Publisher: BioMed Central
• Subject: Animals / Biomedical and Life Sciences / Biomedicine / Cell Communication / Choroid - pathology / Disease Models, Animal / Endothelial Cells - metabolism / Endothelial Cells - pathology / Geographic Atrophy - genetics / Geographic Atrophy - pathology / Humans / Inflammation - genetics / Inflammation - pathology / Macrophages - metabolism / Macrophages - pathology / Macular Degeneration - genetics / Macular Degeneration - pathology / Medicine/Public Health / Mice, Inbred C57BL / NF-kappa B - metabolism / Retinal Pigment Epithelium - pathology / Signal Transduction / Single-Cell Analysis / Translational Ophthalmology