Mapping the origin and fate of myeloid cells in distinct compartments of the eye by single‐cell profiling

Similar to the brain, the eye is considered an immune‐privileged organ where tissue‐resident macrophages provide the major immune cell constituents. However, little is known about spatially restricted macrophage subsets within different eye compartments with regard to their origin, function, and fate during health and disease. Here, we combined single‐cell analysis, fate mapping, parabiosis, and computational modeling to comprehensively examine myeloid subsets in distinct parts of the eye during homeostasis. This approach allowed us to identify myeloid subsets displaying diverse transcriptional states. During choroidal neovascularization, a typical hallmark of neovascular age‐related macular degeneration (AMD), we recognized disease‐specific macrophage subpopulations with distinct molecular signatures. Our results highlight the heterogeneity of myeloid subsets and their dynamics in the eye that provide new insights into the innate immune system in this organ which may offer new therapeutic targets for ophthalmological diseases. The study reveals a substantial heterogeneity of macrophages in distinct compartments of the eye. Microglia represent the predominant cell type in a model of choroidal neovascularization and disease‐associated subpopulations quickly emerge complemented by infiltrating periphery‐derived cells. Single‐cell RNA‐sequencing reveals heterogeneity of macrophages in the cornea, ciliary body and retina under homeostatic conditions.