biostudies-literatureDroho SNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNIAID NIH HHSRheumatology Research FoundationNational Heart, Lung, and Blood InstituteNorthwestern UniversityLupus Research AllianceNational Institute on AgingUnited States-Israel Binational Science FoundationNEI NIH HHSNational Eye InstituteResearch to Prevent BlindnessNational Cancer InstituteNCI NIH HHSNIAMS NIH HHSe168142https://www.ebi.ac.uk/biostudies/studies/S-EPMC10132149biostudies-literatureUnknown8(7)Patients with neovascular AMD (nAMD) suffer vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Macrophages are found in CNV lesions from patients with nAMD. Additionally, Ccr2-/- mice, which lack classical monocyte-derived macrophages, show reduced CNV size. However, macrophages are highly diverse cells that can perform multiple functions. We performed single-cell RNA-Seq on immune cells from WT and Ccr2-/- eyes to uncover macrophage heterogeneity during the laser-induced CNV mouse model of nAMD. We identified 12 macrophage clusters, including Spp1+ macrophages. Spp1+ macrophages were enriched from WT lasered eyes and expressed a proangiogenic transcriptome via multiple pathways, including vascular endothelial growth factor signaling, endothelial cell sprJCI insightCD11c+ macrophages are proangiogenic and necessary for experimental choroidal neovascularization.PMC10132149AG049665EY030923Unrestricted Departmental GrantUH2 AR067687UH2AR067687HL134375Agmt 05/06/14Rheumatology Precision Medicine FundDixon Translational Research Grant Initiative AwardNovel Research GrantInnovative Research AwardP30 CA060553Sybil B. Harrington Career Development Award for Macular DegenerationR01 AI170938K08 EY030923CA060553AR0645462013247Rajesh ALavine JADroho SPerlman HCuda CMfalseCD11c+ macrophages are proangiogenic and necessary for experimental choroidal neovascularization.Patients with neovascular AMD (nAMD) suffer vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Macrophages are found in CNV lesions from patients with nAMD. Additionally, Ccr2-/- mice, which lack classical monocyte-derived macrophages, show reduced CNV size. However, macrophages are highly diverse cells that can perform multiple functions. We performed single-cell RNA-Seq on immune cells from WT and Ccr2-/- eyes to uncover macrophage heterogeneity during the laser-induced CNV mouse model of nAMD. We identified 12 macrophage clusters, including Spp1+ macrophages. Spp1+ macrophages were enriched from WT lasered eyes and expressed a proangiogenic transcriptome via multiple pathways, including vascular endothelial growth factor signaling, endothelial cell spr2023-01-01T00:00:00Z2023 Apr2026-05-29T06:36:15.481Z2025-02-19T02:03:57.06ZS-EPMC101321493682138810.1172/jci.insight.168142