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

EMBO J. 2021 Mar 15;40(6):e105123. doi: 10.15252/embj.2020105123. Epub 2021 Feb 8.

Abstract

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.

Keywords: cornea; macrophages; microglia; retina; single-cell RNA-seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Choroid / blood supply*
  • Choroid / embryology
  • Computational Biology
  • Computer Simulation
  • Eye / cytology
  • Eye / immunology*
  • Eye / metabolism
  • Female
  • Homeostasis / immunology
  • Humans
  • Immunity, Innate / immunology
  • Macrophages / immunology*
  • Macular Degeneration / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / physiology
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism
  • Neovascularization, Physiologic / physiology*
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • Transcription, Genetic / genetics

Associated data

  • GEO/GSE160845
  • GEO/GSE160797