Altered mechanobiology of Schlemm's canal endothelial cells in glaucoma
Altered mechanobiology of Schlemm's canal endothelial cells in glaucoma
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DOI：
10.1073/pnas.1410602111
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发表时间：
2014-09-23
影响因子：
11.1
通讯作者：
Johnson, Mark
中科院分区：
文献类型：
--
作者：
Overby, Darryl R.;Zhou, Enhua H.;Johnson, Mark
流动阻力的增加是青光眼特征的眼压升高的原因，但这种阻力增加的原因尚不清楚。我们测试了施莱姆管（SC）细胞的生物力学行为改变导致这种功能障碍的假设。我们使用原子力显微镜、光磁扭转细胞术和一种独特的细胞灌注仪来检测从健康和青光眼的人SC内壁分离的内皮细胞。在这里，我们确定了青光眼SC细胞中气孔形成倾向降低的存在——这可能是导致流出阻力增加的原因——这与皮质下细胞刚度升高呈正相关，同时对机械微环境的敏感性增强，包括几个关键基因的表达改变，尤其是结缔组织生长因子。而不是被视为一个简单的机械屏障过滤，内皮细胞被视为一种动态材料，其响应机械应变导致孔的形成，从而调节房水流出的阻力。在青光眼中，这一过程受损。总之，这些观察结果支持SC细胞刚度及其对孔隙形成的生物力学效应作为青光眼治疗靶点的观点。
Increased flow resistance is responsible for the elevated intraocular pressure characteristic of glaucoma, but the cause of this resistance increase is not known. We tested the hypothesis that altered biomechanical behavior of Schlemm's canal (SC) cells contributes to this dysfunction. We used atomic force microscopy, optical magnetic twisting cytometry, and a unique cell perfusion apparatus to examine cultured endothelial cells isolated from the inner wall of SC of healthy and glaucomatous human eyes. Here we establish the existence of a reduced tendency for pore formation in the glaucomatous SC cell-likely accounting for increased outflow resistance-that positively correlates with elevated subcortical cell stiffness, along with an enhanced sensitivity to the mechanical microenvironment including altered expression of several key genes, particularly connective tissue growth factor. Rather than being seen as a simple mechanical barrier to filtration, the endothelium of SC is seen instead as a dynamic material whose response to mechanical strain leads to pore formation and thereby modulates the resistance to aqueous humor outflow. In the glaucomatous eye, this process becomes impaired. Together, these observations support the idea of SC cell stiffness-and its biomechanical effects on pore formation-as a therapeutic target in glaucoma.