Regulation of dynamic behavior of retinal microglia by CX3CR1 signaling.
OBJECTIVE
Microglia in the central nervous system display a marked structural dynamism in their processes in the resting state. This dynamic behavior, which may play a constitutive surveying role in the uninjured neural parenchyma, is also highly responsive to tissue injury. The role of CX3CR1, a chemokine receptor expressed in microglia, in regulating microglia morphology and dynamic behavior in the resting state and after laser-induced focal injury was examined.


METHODS
Time-lapse confocal imaging of retinal explants was used to evaluate the dynamic behavior of retinal microglia labeled with green fluorescent protein (GFP). Transgenic mice in which CX3CR1 signaling was ablated (CX3CR1(GFP/GFP)/CX3CR1(-/-)) and preserved (CX3CR1(+/GFP)/CX3CR1(+/-)) were used.


RESULTS
Retinal microglial density, distribution, cellular morphology, and overall retinal tissue anatomy were not altered in young CX3CR1(-/-) animals. In the absence of CX3CR1, retinal microglia continued to exhibit dynamic motility in their processes. However, rates of process movement were significantly decreased, both under resting conditions and in response to tissue injury. In addition, microglia migration occurring in response to focal laser injury was also significantly slowed in microglia lacking CX3CR1.


CONCLUSIONS
CX3CR1 signaling in retinal microglia, though not absolutely required for the presence of microglial dynamism, plays a role in potentiating the rate of retinal microglial process dynamism and cellular migration. CX3CL1 signaling from retinal neurons and endothelial cells likely modulates dynamic microglia behavior so as to influence the level of microglial surveillance under basal conditions and the rate of dynamic behavior in response to tissue injury.
Liang
Katharine J
KJ
Office of the Scientific Director, Division of Epidemiology and Clinical Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lee
Jung Eun
JE
Wang
Yunqing D
YD
Ma
Wenxin
W
Fontainhas
Aurora M
AM
Fariss
Robert N
RN
Wong
Wai T
WT
D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002452:Cell Count; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007834:Lasers / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism*; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000293:injuries; D055351:Retinal Neurons / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D049452:Green Fluorescent Proteins