Actin structure in the outflow tract of normal and glaucomatous eyes

Actin structure in the outflow tract of normal and glaucomatous eyes
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DOI:
10.1016/j.exer.2005.10.025
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发表时间:
2006-06-01
影响因子:
3.4
通讯作者:
Ethier, C. Ross
Ethier, C. Ross
中科院分区:
医学3区
文献类型:
--
作者:
Read, A. Thomas;Chan, Darren W. -H.;Ethier, C. Ross

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目的.目的:研究人眼巩膜外膜管内皮细胞(SCE)和巩膜外膜管组织细胞(JCT)中肌动蛋白(actin)的原位分布,并与正常眼进行比较。新鲜人眼库眼灌注加压固定(n=27只正常眼和22只确诊的青光眼眼)。通过显微切割打开Schlemm管,并标记流出组织用于共聚焦显微镜以使F-肌动蛋白、细胞核、层粘连蛋白和/或CD 31可视化。方法:采用Z序列对Schlemm管内壁、下小管组织和角巩膜外网进行图像采集。在正常的眼睛,内壁Schlemm管内皮(SCE)细胞显示了密集的周边F-肌动蛋白带,如前所述。JCT细胞表现出更随机和无定形的F-肌动蛋白分布。在青光眼的眼睛,周边的F-肌动蛋白带不太常见的内壁SCE细胞,相反,F-肌动蛋白更集中地位于细胞内,出现“纠缠”。这些肌动蛋白缠结在青光眼眼的JCT细胞中也很突出。青光眼的眼睛也表现出具有交联肌动蛋白网络(CLANs)特征的结构,并且更频繁地出现点状肌动蛋白浓度。结果显示,青光眼患者眼内部分区域表现正常,部分区域表现不正常,差异有显著性。人流出道细胞中的F-actin结构在正常眼和青光眼眼之间存在差异,青光眼组织总体上显示出更“无序”的肌动蛋白结构。其中一些变化可能是由于继发于抗青光眼药物给药的影响。我们观察到的大多数变化可能会影响青光眼流出道组织的生物力学特性,但它们在高眼压症发病机制中的作用尚不清楚。(c)2005爱思唯尔有限公司保留所有权利。
Purpose. To characterize the in situ distribution of actin in Schlemm's canal endothelium (SCE) and juxtacanalicular tissue (JCT) cells in glaucomatous human eyes, and compare to the distribution in normal eyes.Methods. Fresh human eye bank eyes were perfused and fixed at pressure (n=27 normal eyes and 22 confirmed glaucomatous eyes). Schlemm's canal was opened by microdissection and outflow tissues were labelled for confocal microscopy to visualize F-actin, nuclei, laminin and/or CD31. Images were acquired in Z-series from the inner wall of Schlemm's canal, juxtacanalicular tissue and outer corneoscleral meshwork.Results. In normal eyes, inner wall Schlemm's canal endothelial (SCE) cells showed a dense peripheral F-actin band, as previously described. JCT cells showed a more random and amorphous F-actin distribution. In glaucoma eyes, peripheral F-actin bands were less common in inner wall SCE cells; instead, F-actin was more centrally located within the cell and appeared 'tangled'. These actin tangles were also prominent in JCT cells of glaucoma eyes. Glaucoma eyes also demonstrated structures with features of cross-linked actin networks (CLANs), and more frequent occurrence of punctuate actin concentrations. There was a significant degree of heterogeneity, with some regions from glaucomatous eyes appearing normal and vice versa.Conclusion. F-actin architecture in human outflow pathway cells in situ differs between normal and glaucoma eyes, with glaucomatous tissue showing a more 'disordered' actin architecture overall. Some of these changes are likely due to effects secondary to administration of antiglaucoma medications. Most of the changes that we observed could potentially affect the biomechanical proper-ties of the outflow pathway tissues in glaucoma, but their role in the pathogenesis of ocular hypertension remains unclear. (c) 2005 Elsevier Ltd. All rights reserved.