Pressure-sensing Piezo1: the eyes have it.
Pressure-sensing Piezo1: the eyes have it.
复制标题
DOI：
10.1113/jp281122
复制
发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Liddle RA
中科院分区：
文献类型：
--
作者：
Swain SM;Liddle RA
眼内压是由机械敏感的小梁网（TM）组织控制的，它调节眼前房房水的流动。眼内压的持续升高是由细胞碎片脱落和TM重塑引起的，通过关节旁和角质层的收缩压力感应细胞，调节房水流入Schlemm管。静息眼内压（7 ~ 15mmhg）通过房水的动态流出维持眼球的正常生长和形状。由于其机械敏感性，TM细胞有能力对眼压的变化作出反应，调节房水的流出，使眼压维持在正常范围内。虽然眼压变化会激活TM细胞中的TRPV4和TREK1等离子通道，但眼压突变触发的机制和TM细胞如何快速反应控制房水流出尚不清楚（Ryskamp et al., 2016; Yarishkin et al., 2018）。Yarishkin和Phuong等人在本期杂志中证明，TM细胞表达机械敏感离子通道Piezo1，其作为直接压力传感器，通过控制房水流出来调节眼压（Yarishkin et al., 2020）。与其他机械激活的非选择性阳离子通道相比，Piezo1是一种快速失活通道。在这项研究中，从关节旁和角膜巩膜区分离的细胞短暂施加压力，96%的细胞产生向内电流。72%的细胞单独呈现快速激活电流，14%的细胞同时呈现快速和慢速激活电流，提示共表达。快速激活电流主要由Piezo1介导，而缓慢、持续的电流需要激活TRPV4。生理性剪切应力增加了Piezo1拮抗剂GsMTx4抑制的细胞内钙水平；但这种变化在很大程度上不受TRPV4拮抗剂HC067047的影响。GsMTx4也抑制压力诱导流出的顺序步骤。因此，尽管Piezo1和TRPV4都在TM细胞中表达，但似乎Piezo1是关节旁和角膜核区细胞快速压力变化的主要换能器，并且在健康的眼睛中可以维持正常的眼内压。
Intraocular pressure is controlled by the mechanosensitive trabecular meshwork (TM) tissue which regulates the flow of aqueous humor in the anterior chamber of the eye. Sustained increases in intraocular pressure result from exfoliation of cell debris and TM remodeling that, through contractile pressure-sensing cells of the juxtacanalicular and corneoscleral regions, regulate the flow of aqueous humor into Schlemm’s canal. Resting intraocular pressures (7 to 15 mm Hg) are maintained for the normal growth and shape of the eye through the dynamic outflow of aqueous humor. By virtue of their mechanosensitivity, TM cells have the ability to respond to changes in intraocular pressure and adjust the outflow of aqueous humor to maintain pressures in a normal range. Although TM cells express ion channels such as TRPV4 and TREK1 which are activated by changes in intraocular pressure, what initiates the response to abrupt pressure changes and how TM cells quickly react to control the outflow of aqueous humor is not clear (Ryskamp et al., 2016; Yarishkin et al., 2018).Yarishkin and Phuong et al., in this issue of the Journal demonstrate that TM cells express the mechanosensitive ion channel Piezo1 which acts as a direct pressure sensor and regulates intraocular pressure by controlling the outflow of aqueous humor (Yarishkin et al., 2020). Piezo1 is a fast inactivating channel compared to other mechanically activated non-selective cation channels. In this study, brief application of pressure on cells isolated from the juxtacanalicular and corneoscleral regions produced an inward current in 96% of cells. 72% of cells exhibited a fast activating current alone, while 14% of cells showed both fast and slow components, suggesting co-expression. The fast activating current was largely mediated by Piezo1 while the slow, sustained current required the activation of TRPV4. Physiological shear stress increased intracellular calcium levels that was inhibited by the Piezo1 antagonist GsMTx4; but this change was largely unaffected by the TRPV4 antagonist HC067047. GsMTx4 also inhibited the sequential steps in pressure-induced outflow. Therefore, although both Piezo1 and TRPV4 are expressed in TM cells, it appears that Piezo1 is the principal transducer of rapid pressure changes in cells of the juxtacanalicular and corneoscleral regions and, in healthy eyes, may maintain normal intraocular pressure.