Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration O’Koren, Emily G. et al. Immunity, Volume 50, Issue 3, 723 - 737.e7
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.
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Funding Info:
This study was funded by Bright Focus MDR (D.R.S.), R01EY021798 (D.R.S.), P30EY005722 (Duke Eye Center), R01EY022959 (V.Y.A.), R01EY026161 (C.B.R.), Bright Focus PFA (M.K.), and Research to Prevent Blindness (Duke Eye Center). F.G. is an EMBO YIP awardee and is supported by SIgN core funding and a Singapore NRF2016NRF-NRFI001-02 grant. We would like to acknowledge the assistance of the Duke Molecular Physiology Institute Molecular Genomics core for the generation of data for the manuscript. We thank S. Finkelstein and E. Lobanova for provision of mice, P. Saloupis for help with OCT, and Y. Hao for TEM (Duke Eye Center). We thank S. Koh (Eroglu lab, Duke) for help with synapse quantification and B. Hogan (Duke) for gifting RosaR26R-fGFP mice.
Description:
The full paper is available for download at the publisher's URL: https://doi.org/10.1016/j.immuni.2019.02.007