Vascular Associations and Dynamic Process Motility in Perivascular Myeloid Cells of the Mouse Choroid: Implications for Function and Senescent Change

Vascular Associations and Dynamic Process Motility in Perivascular Myeloid Cells of the Mouse Choroid: Implications for Function and Senescent Change
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DOI:
10.1167/iovs.13-13522
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发表时间:
2014-03-01
影响因子:
4.4
通讯作者:
Wong, Wai T.
Wong, Wai T.
中科院分区:
医学2区
文献类型:
--
作者:
Kumar, Anil;Zhao, Lian;Wong, Wai T.

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目的。脉络膜的免疫和血管改变与年龄相关性黄斑变性(AMD)有关。由于脉络膜免疫细胞的生理和与脉络膜血管的相互作用尚不完全清楚,我们研究了年轻和老年小鼠脉络膜的髓细胞和血管成分之间的关系。白化病CX3CR1(GFP/+)转基因小鼠,其脉络膜髓样细胞具有绿色荧光,在腔内灌注重要染料DiI来标记脉络膜血管。使用延时共聚焦成像和免疫组织化学分析检查常驻髓样细胞的分布、形态、行为和血管关联。树突状骨髓细胞是脉络膜中大部分的常驻免疫细胞群,它们广泛分布于脉络膜中,并与脉络膜血管密切相关,这些血管随其在血管树中的位置而变化。值得注意的是,与脉络膜动脉和小动脉相关的髓细胞呈细长细胞分布在血管长轴两侧,而与绒毛膜相关的髓细胞呈星状细胞层分布在巩膜上,而不是玻璃体绒毛膜表面。树突样髓细胞在固定位置时表现出快速的过程动力学,非常适合于血管周围空间的综合免疫监测。髓系细胞的密度也随着年龄的增长而增加,这与脉络膜血管的局部衰减有关。常驻髓细胞表现出与脉络膜血管密切但动态的物理相互作用,表明正常脉络膜中存在构成性免疫血管相互作用。这些相互作用可能随着年龄的增长而逐渐改变,为理解AMD背后与年龄相关的脉络膜功能障碍提供了基础。
PURPOSE. Immune and vascular alterations in the choroid are implicated in age-related macular degeneration (AMD). As choroidal immune cells are incompletely understood with regard to their physiology and interactions with choroidal vessels, we examined the associations between myeloid and vascular components of the choroid in young and aged mice.METHODS. Albino CX3CR1(GFP/+) transgenic mice, whose choroidal myeloid cells possess green fluorescence, were perfused intraluminally with the vital dye DiI to label choroidal vessels. The distribution, morphology, behavior, and vascular associations of resident myeloid cells were examined using time-lapse live confocal imaging and immunohistochemical analysis.RESULTS. Dendritiform myeloid cells, comprising most of the resident immune cell population in the choroid, were widely distributed across the choroid and demonstrated close associations with choroidal vessels that varied with their position in the vascular tree. Notably, myeloid cells associated with choroidal arteries and arterioles appeared as elongated cells flanking the long axes of vessels, whereas those associated with the choriocapillaris were distributed as a layer of stellate cells on the scleral but not vitreal choriocapillaris surface. While stationary in position, dendritiform myeloid cells demonstrated the rapid process dynamism well suited to comprehensive immunosurveillance of the perivascular space. Myeloid cells also increased in density as a function of aging, correlating locally with greater choroidal vascular attenuation.CONCLUSIONS. Resident myeloid cells demonstrated close but dynamic physical interactions with choroidal vessels, indicative of constitutive immune-vascular interactions in the normal choroid. These interactions may alter progressively with aging, providing a basis for understanding age-related choroidal dysfunction underlying AMD.