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

Area of Science:

• Neuroscience
• Immunology
• Ophthalmology

Background:

• Microglia, the resident immune cells of the central nervous system, are known to repopulate after ablation.
• The functional capacity and regulatory mechanisms of these repopulated microglia remain largely uncharacterized.

Purpose of the Study:

• To investigate microglial homeostasis, repopulation dynamics, and functional recovery in the adult mouse retina.
• To elucidate the molecular mechanisms governing microglial repopulation and their role in maintaining retinal integrity.

Main Methods:

• Utilized in vivo imaging and cell-fate mapping techniques in adult mouse retinas.
• Examined microglial distribution, morphology, and function following ablation.
• Investigated the role of CX3CL1-CX3CR1 signaling in regulating microglial repopulation.

Main Results:

• Discovered that repopulation originates from residual microglia in the central retina, which proliferate and migrate centrifugally.
• Demonstrated that repopulated microglia fully restore normal distributions, morphologies, and functions, including surveying behaviors and responses to injury.
• Identified CX3CL1-CX3CR1 signaling as a key regulator, with deficiency slowing and exogenous CX3CL1 accelerating repopulation.

Conclusions:

• Microglial repopulation effectively restores organization and function after perturbation in the retina.
• Chemokine signaling between neurons and microglia is crucial for regulating microglial homeostasis and recovery.