Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm's Canal Endothelia.
Enhancement of Outflow Facility in the Murine Eye by Targeting Selected Tight-Junctions of Schlemm's Canal Endothelia.
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DOI：
10.1038/srep40717
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发表时间：
2017-01-16
影响因子：
4.6
通讯作者：
Humphries P
中科院分区：
文献类型：
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作者：
Tam LC;Reina-Torres E;Sherwood JM;Cassidy PS;Crosbie DE;Lütjen-Drecoll E;Flügel-Koch C;Perkumas K;Humphries MM;Kiang AS;O'Callaghan J;Callanan JJ;Read AT;Ethier CR;O'Brien C;Lawrence M;Campbell M;Stamer WD;Overby DR;Humphries P
小梁网的前小管结缔组织与施累姆氏管（SC）的内壁内皮一起提供了对前房流出液的大部分阻力。内皮细胞内衬SC精心制作紧密连接（TJ），下调可能会扩大细胞间的细胞旁空间，允许更多的液体流出。我们观察到，在人SC内皮单层中，在siRNA介导的TJ转录物、紧密连接蛋白-11、闭锁小带-1（ZO-1）和三纤维素的抑制后，细胞旁通透性显著增加。在小鼠中未检测到claudin-11，但前房内注射靶向ZO-1和tricellulin的siRNA显著增加了流出便利性。通过透射电子显微镜对SC内壁进行的结构定性和定量分析显示，与非靶向siRNA相比，靶向siRNA处理的内皮细胞之间的开放裂缝明显更多。这些数据证实了SC内皮的连续性是流出阻力的重要决定因素的概念，并表明SC内皮TJ代表了通过常规流出系统增强水运动的特定目标。
The juxtacanalicular connective tissue of the trabecular meshwork together with inner wall endothelium of Schlemm’s canal (SC) provide the bulk of resistance to aqueous outflow from the anterior chamber. Endothelial cells lining SC elaborate tight junctions (TJs), down-regulation of which may widen paracellular spaces between cells, allowing greater fluid outflow. We observed significant increase in paracellular permeability following siRNA-mediated suppression of TJ transcripts, claudin-11, zonula-occludens-1 (ZO-1) and tricellulin in human SC endothelial monolayers. In mice claudin-11 was not detected, but intracameral injection of siRNAs targeting ZO-1 and tricellulin increased outflow facility significantly. Structural qualitative and quantitative analysis of SC inner wall by transmission electron microscopy revealed significantly more open clefts between endothelial cells treated with targeting, as opposed to non-targeting siRNA. These data substantiate the concept that the continuity of SC endothelium is an important determinant of outflow resistance, and suggest that SC endothelial TJs represent a specific target for enhancement of aqueous movement through the conventional outflow system.