Effects of atorvastatin on porcine aqueous humour outflow and trabecular meshwork cells.
Effects of atorvastatin on porcine aqueous humour outflow and trabecular meshwork cells.
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DOI：
10.3892/etm.2017.5353
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发表时间：
2018-01
影响因子：
2.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Cong L;Fu S;Zhang J;Zhao J;Zhang Y
原发性开角型青光眼（Primary open-angle glaucoma，POAG）是致盲的主要原因之一，其发病机制复杂。广泛认为POAG的主要原因是小梁网（TM）的失调，其调节对房水流出的阻力。随着传统途径（由TM和施累姆氏管组成）中流出阻力的增加，眼内压升高。TM是由细胞外基质（例如，胶原），其中大部分组织成由内皮样小梁细胞覆盖的梁网络。目前，缺乏有效的抗青光眼药物作用于TM正常化小梁流出是POAG治疗的瓶颈。阿托伐他汀是一种降血脂药物，已被证明对POAG有益。本研究的目的是探讨阿托伐他汀对TM的可能的作用机制，通过使用在体内的猪房水流出模型和TM细胞在体外。用阿托伐他汀（50-200 µM）灌注去核猪眼2 h可增加房水流出量（P<0.05，n=6），这可能是通过调节TM细胞的形态和细胞骨架的分布。阿托伐他汀在mRNA和蛋白水平降低粘附分子。在浓度<100 µM时，未观察到阿托伐他汀对TM细胞的细胞毒性。只有当阿托伐他汀浓度<100 µM时，上述阿托伐他汀诱导的效应在去除化合物后才可逆。目前的研究表明，阿托伐他汀有效地提高房水流出，可能是由于影响TM细胞形态，细胞骨架和细胞连接。他汀类药物可能是POAG潜在的降眼压药物。
Primary open-angle glaucoma (POAG) with complex pathogenesis is one of the many major causes of blindness. It is widely accepted that the major cause of POAG is the dysregulation of the trabecular meshwork (TM), which regulates the resistance to aqueous humour outflow. Intraocular pressure is elevated with increasing outflow resistance in the conventional pathway, which consists of the TM and Schlemm's canal. The TM is a filter made up of extracellular matrix (e.g., collagens), most of which is organized into a network of beams covered by endothelial-like trabecular cells. Currently, lack of effective anti-glaucoma drugs acting on TM to normalize trabecular outflow represents a bottleneck for POAG therapy. Atorvastatin, a lipid-lowering drug, has been proven to be of benefit for POAG. The present study aimed to investigate the possible mechanisms of action of atorvastatin on the TM by using a porcine aqueous humour outflow model in vivo and TM cells in vitro. Perfusion of enucleated porcine eyes with atorvastatin (50–200 µM) for 2 h increased aqueous humour outflow (P<0.05, n=6), possibly via regulating the morphology of TM cells and the distribution of the cytoskeleton. Atorvastatin decreased adhesion molecules at the mRNA and protein level. No cytotoxicity of atorvastatin on TM cells was observed at concentrations of <100 µM. The atorvastatin-induced effects mentioned above were reversible after removal of the compound only if the atorvastatin concentration was <100 µM. The present study demonstrated that atorvastatin efficaciously elevated aqueous humour outflow, possibly due to affecting TM-cell morphology, cytoskeleton and cell junctions. Statins may be potential therapeutic agents for lowering intraocular pressure in POAG.
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DOI：
10.1007/s004170000252
发表时间：
2001-03-01
影响因子：
2.7
作者：
Picht, G;Welge-Luessen, U;Lütjen-Drecoll, E
通讯作者：
Lütjen-Drecoll, E
影响因子：
4.4
作者：
Haddadin, Ramez I.;Oh, Dong-Jin;Rhee, Douglas J.
通讯作者：
Rhee, Douglas J.
影响因子：
3.4
作者：
Khurana, RN;Deng, PF;Rao, PV
通讯作者：
Rao, PV
影响因子：
3.4
作者：
Hu, Yujie;Gabelt, B'Ann True;Kaufman, Paul L.
通讯作者：
Kaufman, Paul L.
流出阻力产生的不断变化的范式：朝向JCT和内壁内皮的协同模型。
影响因子：
3.4
作者：
Overby, Darryl R.;Stamer, W. Daniel;Johnson, Mark
通讯作者：
Johnson, Mark