Macular and peripheral distribution of ICAM-1 in the human choriocapillaris and retina.

Macular and peripheral distribution of ICAM-1 in the human choriocapillaris and retina.
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发表时间:
2006-03
期刊:
影响因子:
2.2
通讯作者:
R. Mullins;Jessica M. Skeie;E. A. Malone;M. Kuehn
R. Mullins;Jessica M. Skeie;E. A. Malone;M. Kuehn
中科院分区:
医学4区
文献类型:
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作者:
R. Mullins;Jessica M. Skeie;E. A. Malone;M. Kuehn

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目的:为了了解人眼不同地形区域绒毛膜毛细血管内皮细胞的激活程度,我们试图比较细胞间粘附分子-1 (ICAM-1)在人眼黄斑区和周围区域的定位。方法采用单克隆抗体和多克隆抗体检测糖包埋人供眼(黄斑和锯齿眼)ICAM-1和ICAM-2的免疫反应性。观察20只眼外周区和黄斑区的ICAM-1标记模式。使用ImageJ软件对9只眼的黄斑和黄斑外穿孔进行毛膜毛抗icam -1标记强度的形态计量学分析。对来自同一只眼睛同一区域的rpe -脉络膜进行ICAM-1 mRNA的定量PCR分析,并对n -糖苷酶处理或未处理的样品进行Western blot比较视网膜和脉络膜ICAM-1。结果:ICAM-1在人供体眼黄斑处的标记明显强于周围脉络膜(14/20)。在绒毛膜毛细血管和视网膜血管中也检测到ICAM-2。形态学测量证实,9只眼中有6只眼的ICAM-1与黄斑外有显著差异(p<0.05), 9只眼中有1只眼的ICAM-1表现相反的模式。内源性碱性磷酸酶或ICAM-2没有发现这种模式。外限制膜(ELM)的情况正好相反,远周的ICAM-1标记比黄斑更强烈。在Western blots上,脉络膜ICAM-1表现出比视网膜形式更大的分子量,大部分明显的重量差异是由于n链碳水化合物链。结论绒毛毛细血管内ICAM-1分布的区域差异可能表明该区域受白细胞运输增加的影响。鉴于炎症过程在年龄相关性黄斑变性(AMD)中的作用,我们提出黄斑毛毛纤维中较高水平的ICAM-1蛋白可能使黄斑对AMD中免疫细胞介导的损伤更敏感。
PURPOSE In order to understand the extent of choriocapillary endothelial cell activation in different topographic regions of the eye, we sought to compare the localization of intercellular adhesion molecule-1 (ICAM-1) in macular and peripheral regions of human eyes. METHODS Sections of sucrose-embedded human donor eyes that included the macula and ora serrata were evaluated for ICAM-1 and ICAM-2 immunoreactivity with monoclonal and polyclonal antibodies. Patterns of ICAM-1 labeling in peripheral and macular regions were examined in 20 eyes. Morphometric analyses of anti-ICAM-1 labeling intensity in the choriocapillaris were performed using ImageJ software on a series of macular and extramacular punches from nine eyes. Quantitative PCR analysis for ICAM-1 mRNA was performed on the RPE-choroid from the same regions from six of the same eyes, and Western blots of samples treated or untreated with N-glycosidase were performed to compare retinal and choroidal ICAM-1. RESULTS ICAM-1 labeling of the choriocapillaris was typically more intense in the macula than in the peripheral choroid in human donor eyes (14/20). ICAM-2 was also detected in the choriocapillaris and retinal vessels. Morphometric measurements confirmed a significant macular-extramacular difference in ICAM-1 in six of nine eyes (p<0.05), with 1 of 9 eyes showing the opposite pattern. This pattern was not noted for endogenous alkaline phosphatase or ICAM-2. The opposite pattern was noted in the external limiting membrane (ELM), which exhibited more intense ICAM-1 labeling in the far periphery than in the macula. On Western blots, choroidal ICAM-1 exhibited a greater molecular weight than the retinal form, with most of the apparent weight difference due to N-linked carbohydrate chains. CONCLUSIONS The regional differences in ICAM-1 distribution in the choriocapillaris may indicate that this region is subject to increased leukocyte trafficking. In view of the role of inflammatory processes in age-related macular degeneration (AMD), we propose that the higher level of ICAM-1 protein in the macular choriocapillaris may impart greater susceptibility of the macula to immune cell-mediated damage in AMD.