Srinivas Sangly P
*PhD School of Optometry, Indiana University, Bloomington, Indiana.
Optom Vis Sci. 2010 Apr;87(4):E239-54. doi: 10.1097/OPX.0b013e3181d39464.
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 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 tight junctions) of the endothelium is sensitive to remodeling of its peri-junctional actomyosin ring, 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 peri-junctional actomyosin ring 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.
角膜内皮维持基质的脱水状态，这是角膜透明的先决条件。基质脱水的主要挑战是与基质中亲水性糖胺聚糖相关的肿胀压力。这种负压促使液体从前房渗入基质，但渗漏速率受到内皮紧密连接的限制。内皮的这一作用体现了其屏障功能。在健康角膜中，液体渗漏通过与内皮自身相关的主动液体泵机制得以平衡。尽管这种泵 - 渗漏假说是几十年前提出的，但泵功能和渗漏功能之间平衡调节的潜在机制仍 largely 未知。在过去几十年中，已发现支持液体泵活动的离子转运系统。相比之下，尽管有大量证据表明内皮屏障功能障碍会导致角膜水肿，但其调节的分子层面相对未知。然而，我们实验室最近的研究结果表明，内皮的屏障完整性（即紧密连接的结构和功能完整性）对其位于顶端连接复合体的连接周肌动球蛋白环的重塑敏感。本综述聚焦于内皮屏障完整性的动态调节，涉及连接周肌动球蛋白环的可塑性及其与 Rho 家族小 GTP 酶下游细胞信号传导的关联。基于目前的研究结果，似乎在不久的将来有可能开发出针对炎症应激引起的角膜水肿的特异性药物治疗策略。
