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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. SYNOPSIS: 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 several macrophage subsets in the cornea, ciliary body and retina under homeostatic conditions.•Embryonic fate mapping reveals prenatal origin of macrophages in the retina, ciliary body and cornea.•Significant homeostatic turnover was only detectable for cornea macrophages by the use of several models targeting the definitive hematopoiesis.•Microglia are the predominant myeloid cell type in choroidal neovascularization and create context‐specific disease‐associated microglia subsets. [ABSTRACT FROM AUTHOR]

Recent studies have shown that tissue macrophages (MΦ) arise from embryonic progenitors of the yolk sac ( YS) and fetal liver and colonize tissues before birth. Further studies have proposed that developmentally distinct tissue MΦ can be identified based on the differential expression of F4/80 and CD11b, but whether a characteristic transcriptional profile exists is largely unknown. Here, we took advantage of an inducible fate-mapping system that facilitated the identification of CD45+c-kit− CX3 CR1+F4/80+ (A2) progenitors of the YS as the source of F4/80hi but not CD11bhi MΦ. Large-scale transcriptional profiling of MΦ precursors from the YS stage to adulthood allowed for building computational models for F4/80hi tissue macrophages being direct descendants of A2 progenitors. We further identified a distinct molecular signature of F4/80hi and CD11bhi MΦ and found that Irf8 was vital for MΦ maturation. Our data provide new cellular and molecular insights into the origin and developmental pathways of tissue MΦ. [ABSTRACT FROM AUTHOR]

Background Emerging evidence has highlighted the pivotal role of the immune system in neurodegenerative diseases. This study investigated the impact of progressive neurodegeneration on the differentiation and development of hematopoietic stem cells in the peripheral blood of Parkinson's patients. Methods: A colony-forming cell assay was established to study hematopoietic stem cells from venous blood of Parkinson's patients, and flow cytometry was used to analyze the expression of chemokine receptors on monocytes. Results We demonstrate that there is strong upregulation in the percentage of monocyte precursors in the peripheral blood of Parkinson's patients and asymptomatic high-risk individuals. We identify the receptor CCR2 as undergoing strong upregulation on the surface of classical monocytes in Parkinson's patients. Conclusions The association between blood cell development and progressive cell death in the brain of Parkinson's patients should be further investigated as a potential dynamic biomarker and indicator of disease progression. © 2013 Movement Disorder Society [ABSTRACT FROM AUTHOR]