Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm's canal endothelial cells.
Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm's canal endothelial cells.
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DOI：
10.1038/srep19640
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发表时间：
2016-01-19
影响因子：
4.6
通讯作者：
Tanihara H
中科院分区：
文献类型：
--
作者：
Kaneko Y;Ohta M;Inoue T;Mizuno K;Isobe T;Tanabe S;Tanihara H
盐酸利帕舒地尔水合物（K-115）是一种特异性Rho相关卷曲螺旋蛋白激酶（ROCK）抑制剂，是日本开发的第一种用于治疗青光眼和高眼压症的滴眼液。局部给予K-115可降低兔的眼内压（IOP）并增加流出功能。本研究评价了K-115对猴小梁网（TM）细胞和Schlemm管内皮（SCE）细胞的影响。K-115诱导的收缩和圆形的细胞体，以及破坏肌动蛋白束在TM细胞。在SCE细胞单层渗透性研究中，K-115显著降低了跨内皮电阻（TEER），并增加了FITC-葡聚糖的跨内皮通量。此外，K-115破坏了SCE细胞单层中ZO-1表达的细胞定位。这些结果表明，K-115通过增加与TM细胞行为调节相关的外流便利性和与紧密连接破坏相关的SCE细胞渗透性来降低IOP。
Ripasudil hydrochloride hydrate (K-115), a specific Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor, was the first ophthalmic solution developed for the treatment of glaucoma and ocular hypertension in Japan. Topical administration of K-115 decreased intraocular pressure (IOP) and increased outflow facility in rabbits. This study evaluated the effect of K-115 on monkey trabecular meshwork (TM) cells and Schlemm’s canal endothelial (SCE) cells. K-115 induced retraction and rounding of cell bodies as well as disruption of actin bundles in TM cells. In SCE-cell monolayer permeability studies, K-115 significantly decreased transendothelial electrical resistance (TEER) and increased the transendothelial flux of FITC-dextran. Further, K-115 disrupted cellular localization of ZO-1 expression in SCE-cell monolayers. These results indicate that K-115 decreases IOP by increasing outflow facility in association with the modulation of TM cell behavior and SCE cell permeability in association with disruption of tight junction.