Dynamic regulation of barrier integrity of the corneal endothelium.
Dynamic regulation of barrier integrity of the corneal endothelium.
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DOI：
10.1097/opx.0b013e3181d39464
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Srinivas SP
中科院分区：
文献类型：
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作者：
Srinivas SP
角膜内皮维持基质去肿胀，这是角膜透明的先决条件。基质去肿胀的主要挑战是与基质中亲水性糖胺聚糖相关的膨胀压力。这种负压导致液体从前房渗漏到基质中，但渗漏速率受到内皮紧密连接（TJ）的限制。内皮的这种作用代表了其屏障功能。在健康的角膜中，液体渗漏通过与内皮本身相关的主动液体泵机制来平衡。尽管这种泵泄漏假说是几十年前提出的，但泵和泄漏功能之间平衡调节的机制仍然很大程度上未知。在过去的几十年里，支持流体泵活动的离子传输系统被发现。相比之下，尽管有大量证据表明角膜水肿继发于内皮屏障功能障碍，但其调节背后的分子方面却相对未知。然而，我们实验室的最新研究结果表明，内皮细胞的屏障完整性（即 TJ 的结构和功能完整性）对其位于顶端连接复合体的连接周围肌动球蛋白环 (PAMR) 的重塑敏感。这篇综述提供了关于内皮屏障完整性相对于 PAMR 可塑性的动态调节及其与 Rho 家族小 GTPase 下游细胞信号传导的关联的重点视角。根据迄今为止的研究结果，似乎在不久的将来可能会开发出特定的药理学策略来治疗炎症应激引起的角膜水肿。
The corneal endothelium maintains stromal deturgescence, which is a prerequisite for corneal transparency. The principal challenge to stromal deturgescence is the swelling pressure associated with the hydrophilic glycosaminoglycans in the stroma. This negative pressure induces fluid leak into the stroma from the anterior chamber, but the rate of leak is restrained by the tight junctions (TJs) of the endothelium. This role of the endothelium represents its barrier function. In healthy cornea, the fluid leak is counterbalanced by an active fluid pump mechanism associated with the endothelium itself. Although this Pump-Leak hypothesis was postulated several decades ago, the mechanisms underlying regulation of the balance between the pump and leak functions remain largely unknown. In the last couple of decades, the ion transport systems that support the fluid pump activity have been discovered. In contrast, despite significant evidence for corneal edema secondary to endothelial barrier dysfunction, the molecular aspects underlying its regulation are relatively unknown. Recent findings in our laboratory, however, indicate that barrier integrity (i.e., structural and functional integrity of the TJs) of the endothelium is sensitive to remodeling of its peri-junctional actomyosin ring (PAMR), which is located at the apical junctional complex. This review provides a focused perspective on dynamic regulation of the barrier integrity of endothelium vis-à-vis plasticity of the PAMR and its association with cell signaling downstream of small GTPases of the Rho family. Based on findings to date, it appears that development of specific pharmacological strategies to treat corneal edema in response to inflammatory stress would be possible in the near future.