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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • O'Koren, EG; Yu, C; Klingeborn, M; Wong, AYW; Prigge, CL; Mathew, R; Kalnitsky, J; Msallam, RA; Silvin, A; Kay, JN; Bowes Rickman, C; Arshavsky, VY; Ginhoux, F; Merad, M; Saban, DR

Published Date

  • March 5, 2019

Published In

Volume / Issue

  • 50 / 3

Start / End Page

  • 723 - 737.e7

PubMed ID

  • 30850344

Pubmed Central ID

  • 30850344

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2019.02.007

Language

  • eng