Liang Katharine J, Lee Jung Eun, Wang Yunqing D, Ma Wenxin, Fontainhas Aurora M, Fariss Robert N, Wong Wai T
Office of the Scientific Director, Division of Epidemiology and Clinical Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4444-51. doi: 10.1167/iovs.08-3357. Epub 2009 May 14.
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.
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.
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.
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.
中枢神经系统中的小胶质细胞在静息状态下其突起表现出显著的结构动态性。这种动态行为可能在未受损的神经实质中发挥组成性监测作用，对组织损伤也高度敏感。研究了小胶质细胞中表达的趋化因子受体CX3CR1在调节静息状态下以及激光诱导局灶性损伤后小胶质细胞形态和动态行为中的作用。
利用视网膜外植体的延时共聚焦成像来评估用绿色荧光蛋白（GFP）标记的视网膜小胶质细胞的动态行为。使用CX3CR1信号被消除（CX3CR1(GFP/GFP)/CX3CR1(-/-)）和保留（CX3CR1(+/GFP)/CX3CR1(+/-)）的转基因小鼠。
年轻的CX3CR1(-/-)动物的视网膜小胶质细胞密度、分布、细胞形态和整个视网膜组织解剖结构未发生改变。在缺乏CX3CR1的情况下，视网膜小胶质细胞在其突起中继续表现出动态运动性。然而，无论是在静息条件下还是对组织损伤的反应中，突起运动速率均显著降低。此外，在缺乏CX3CR1的小胶质细胞中，对局灶性激光损伤产生的小胶质细胞迁移也显著减慢。
视网膜小胶质细胞中的CX3CR1信号，虽然对于小胶质细胞动态性的存在不是绝对必需的，但在增强视网膜小胶质细胞突起动态性速率和细胞迁移方面发挥作用。来自视网膜神经元和内皮细胞的CX3CL1信号可能调节小胶质细胞的动态行为，从而影响基础条件下小胶质细胞监测水平以及对组织损伤的动态行为速率。
