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W. T. Wong, K. J. Liang, J. Lee, Y. D. Wang, R. N. Fariss; Dynamic Behavior in Retinal Microglia Is Regulated by CX3CR1 Signaling. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3033.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal microglia display a marked structural dynamism of their processes in the resting state. This dynamic behavior, thought to play a constitutive surveillance role in the neural parenchyma, is also highly responsive to tissue injury. The molecular signals exchanged between retinal microglia and surrounding neurons and macroglia in regulating microglial dynamism are incompletely understood. CX3CR1 is a chemokine receptor specifically expressed on microglia and its ligand, CX3CL1 is expressed by both retinal neurons and endothelial cells. We evaluated the contribution of CX3CR1 in regulating microglia morphology and dynamic behavior in both the resting state and after laser-induced focal injury.
Transgenic CX3CR1 +/GFP and CX3CR1 GFP/GFP mice in which CX3CR1 signaling has been preserved and ablated respectively were employed. Retinal explants were acutely isolated and live tissue time-lapse confocal imaging was used to visualize the microglial dynamics under resting and following laser injury in presence and absence of CX3CR1 signaling.
Retinal microglia are sensitive to exogenous CX3CL1 and alter their morphology reversibly in response to CX3CL1 application. Dynamic behavior however is not completely dependent on CX3CR1 signaling as process motility and cell migration continues to occur in both the presence and the absence of CX3CR1. Quantitative analysis revealed that CX3CR1 does play a signaling modulatory role in regulating dynamic behavior in microglia. Motilityof processes of microglia lacking CX3CR1 were significantly slower, and were less responsive to injury compared to those in which CX3CR1 signaling is preserved. Migratory behavior following laser injury was also decreased in the absence of CX3CR1.
Our findings indicate that neuronally-derived chemokine signaling onto retinal microglia, of which CX3CR1 is an example, plays a significant modulatory role in regulating dynamic microglia behavior under steady state conditions, and may thus influence the level of microglial surveillance of neural parenchyma and microglial responses to tissue insults. These results clarify the physiological regulation of microglial behavior and can help illuminate the functional roles that microglia play in health and disease.
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