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Immunity. 2019 Mar 19;50(3):723-737.e7. doi: 10.1016/j.immuni.2019.02.007. Epub 2019 Mar 5.

Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration.

Author information

1
Department of Ophthalmology, Duke University, Durham, NC 27710, USA.
2
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
3
Department of Neurobiology, Duke University, Durham, NC 27710, USA.
4
Department of Ophthalmology, Duke University, Durham, NC 27710, USA; Department of Neurobiology, Duke University, Durham, NC 27710, USA.
5
Department of Ophthalmology, Duke University, Durham, NC 27710, USA; Department of Cell Biology, Duke University, Durham, NC 27710, USA.
6
Department of Ophthalmology, Duke University, Durham, NC 27710, USA; Department of Pharmacology, Duke University, Durham, NC 27710, USA.
7
Precision Immunology Institute and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
8
Department of Ophthalmology, Duke University, Durham, NC 27710, USA; Department of Immunology, Duke University, Durham, NC 27710, USA. Electronic address: daniel.saban@duke.edu.

Abstract

Microglia from different nervous system regions are molecularly and anatomically distinct, but whether they also have different functions is unknown. We combined lineage tracing, single-cell transcriptomics, and electrophysiology of the mouse retina and showed that adult retinal microglia shared a common developmental lineage and were long-lived but resided in two distinct niches. Microglia in these niches differed in their interleukin-34 dependency and functional contribution to visual-information processing. During certain retinal-degeneration models, microglia from both pools relocated to the subretinal space, an inducible disease-associated niche that was poorly accessible to monocyte-derived cells. This microglial transition involved transcriptional reprogramming of microglia, characterized by reduced expression of homeostatic checkpoint genes and upregulation of injury-responsive genes. This transition was associated with protection of the retinal pigmented epithelium from damage caused by disease. Together, our data demonstrate that microglial function varies by retinal niche, thereby shedding light on the significance of microglia heterogeneity.

KEYWORDS:

IL-34; macrophages; microglia; microglial heterogeneity; phagocytes; retinal degeneration; retinitis pigmentosa

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