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Updated: Jun 18, 2026
Digestion of Whole Mouse Eyes for Multi-Parameter Flow Cytometric Analysis of Mononuclear Phagocytes
Published on: June 17, 2020
Single-cell and spatial analyses reveal endothelial-macrophage inflammatory crosstalk in dry age-related macular
Yujie Chen1, Chuling Liu1, Jinghan Chen1
1Medical School, Shenzhen University, Shenzhen, China.
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.
Insights
Immune cells, particularly SLC16A10-positive macrophages, are key in dry age-related macular degeneration (AMD). An endothelial-macrophage pathway involving TNFSF10-TNFRSF10B and NF-κB signaling drives disease progression.
Area of Science:
- Ophthalmology
- Immunology
- Genomics
Background:
- Dry age-related macular degeneration (AMD) involves retinal pigment epithelium-choroid degeneration and immune dysregulation.
- The precise cellular interactions and regulatory mechanisms of macrophage activation in dry AMD are not fully understood.
Purpose of the Study:
- To investigate immune remodeling in the RPE-choroid region of dry AMD.
- To identify cellular interactions and signaling pathways driving macrophage activation and disease progression in dry AMD.
Main Methods:
- Integrated spatial transcriptomics and single-cell RNA sequencing from mouse models and human dry AMD samples.
- Bioinformatic analyses including cell-cell communication, enrichment, and pseudotime trajectory analyses were performed.
Main Results:
- Myeloid cell infiltration was observed in the RPE-choroid region of a mouse model.
- SLC16A10-positive macrophages with pro-inflammatory features were enriched in human dry AMD samples.
- Endothelial cells regulate these macrophages via the TNFSF10-TNFRSF10B pathway, activating NF-κB signaling and promoting a vascular-immune inflammatory niche.
Conclusions:
- This study systematically characterizes immune remodeling in the RPE-choroid region in dry AMD.
- An endothelial-macrophage TNFSF10-TNFRSF10B-NF-κB signaling pathway was identified as a driver of dry AMD progression.
- These findings offer novel insights into dry AMD mechanisms and potential therapeutic targets.
