A myosin light chain kinase inhibitor, ML-9, lowers the intraocular pressure in rabbit eyes
A myosin light chain kinase inhibitor, ML-9, lowers the intraocular pressure in rabbit eyes
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DOI：
10.1006/exer.2002.2009
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发表时间：
2002-08-01
影响因子：
3.4
通讯作者：
Tanihara, H
中科院分区：
文献类型：
--
作者：
Honjo, M;Inatani, M;Tanihara, H
研究了肌球蛋白轻链激酶（MLCK）在调节兔眼眼内压（IOP）和流出能力中的作用。在前房内和玻璃体内注射 ML-9（一种特异性 MLCK 抑制剂）之前和之后测定眼压和瞳孔直径。前房内施用ML-9后3小时测定总流出设施和葡萄膜巩膜流出设施。进行免疫印迹以鉴定人小梁网 (TM) 细胞中的 MLCK 和肌球蛋白 (MLC) 亚型的 20 kDa 轻链。 ML-9处理后检查MIC的磷酸化状态。还研究了ML-9对培养的TM细胞的形态以及肌动蛋白和纽蛋白分布的影响。在兔眼中，给予 ML-9 会导致 IOP 呈剂量依赖性下降。还观察到流出设施有所增加。免疫印迹分析揭示了人类 TM 细胞中存在 MLCK。暴露于 ML-9 会剂量依赖性地抑制 MLC 磷酸化/激活。抑制剂。引起细胞收缩和解离、肌动蛋白束破坏以及 TM 细胞粘着斑形成受损。 ML-9 会降低兔眼的眼压并增加流出能力。眼压降低效应可能与 TM 细胞形状的改变有关。 MLCK 抑制剂有可能被开发成治疗青光眼的新型药物。 (C) 2002 爱思唯尔科学有限公司。
The role of myosin light chain kinase (MLCK) in regulating the intraocular pressure (IOP) and outflow facility in rabbit eyes were studied. The IOP and pupil diameter were determined before and after intracameral and intravitreal administration of ML-9, a specific MLCK inhibitor. Total outflow facility and uveoscleral outflow facility was determined 3 hr after intracameral administration of ML-9. Immunoblotting was performed to identify MLCK and the 20-kDa light chain of myosin (MLC) isoforms in human trabecular meshwork (TM) cells. The phosphorylation status of MIC was examined following ML-9 treatment. The effects of ML-9 on the morphology and actin and vinculin distribution in cultured TM cells were also studied. In rabbit eyes, administration of ML-9 resulted in a dose-dependent decrease in IOP. An increase of the outflow facility was also observed. Immunoblot analysis revealed the presence of MLCK in human TM cells. Exposure to ML-9 dose-dependently inhibited MLC phosphorylation/activation. The inhibitor. caused retraction and dissociation of cells, disruption of actin bundles and impairment of focal adhesion formation in TM cells. ML-9 induces a reduction in IOP and an increase in the outflow facility in rabbit eyes. The IOP-lowering effects may be related to alterations in TM cell shapes. Inhibitors of MLCK may potentially be developed into novel medications for glaucoma. (C) 2002 Elsevier Science Ltd.