Immunity
Volume 50, Issue 3, 19 March 2019, Pages 723-737.e7
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Article
Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration

https://doi.org/10.1016/j.immuni.2019.02.007Get rights and content
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Highlights

  • Retina has 2 microglia pools differing by niche and IL-34 dependency

  • In homeostasis, IL-34-dependent microglia contribute to neuronal function

  • In degeneration, both pools relocate toward the retinal pigmented epithelium (RPE)

  • This transition reprograms microglia and is associated with RPE protection

Summary

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

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

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8

These authors contributed equally

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