Repopulating retinal microglia restore endogenous organization and function under CX3CL1-CX3CR1 regulation

Science Advances
Yikui ZhangWai T Wong

Abstract

Microglia have been discovered to undergo repopulation following ablation. However, the functionality of repopulated microglia and the mechanisms regulating microglia repopulation are unknown. We examined microglial homeostasis in the adult mouse retina, a specialized neural compartment containing regular arrays of microglia in discrete synaptic laminae that can be directly visualized. Using in vivo imaging and cell-fate mapping techniques, we discovered that repopulation originated from residual microglia proliferating in the central inner retina that subsequently spread by centrifugal migration to fully recapitulate pre-existing microglial distributions and morphologies. Repopulating cells fully restored microglial functions including constitutive "surveying" process movements, behavioral and physiological responses to retinal injury, and maintenance of synaptic structure and function. Microglial repopulation was regulated by CX3CL1-CX3CR1 signaling, slowing in CX3CR1 deficiency and accelerating with exogenous CX3CL1 administration. Microglial homeostasis following perturbation can fully recover microglial organization and function under the regulation of chemokine signaling between neurons and microglia.

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Methods Mentioned

BETA
transgenic
confocal microscopy
enzyme-linked immunosorbent assay
Protein Assay
electron
transmission electron microscopy

Software Mentioned

xPONENT
GraphPad
Bitplane
EdgeR
ERG Data Analyzer
HTSeq
NIH ImageJ
ImageJ
Imaris
TopHat

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