Civan Mortimer M, Macknight Anthony D C
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Exp Eye Res. 2004 Mar;78(3):625-31. doi: 10.1016/j.exer.2003.09.021.
The intraocular pressure (IOP) reflects a balance between inflow and outflow of aqueous humour. A major strategy in the medical treatment of glaucoma is to reduce inflow and thereby IOP. Understanding the mechanisms and regulation of inflow is thus of clear clinical relevance. Many mechanisms underlying inflow have been identified. The integration and regulation of these mechanisms is less clear. Aqueous humour is secreted across the ciliary epithelium by transferring solute, chiefly NaCl, from the stroma to the posterior chamber of the eye, with water passively following. The epithelium consists of two layers: the pigmented ciliary epithelial (PE) cells abutting the stroma, and the non-pigmented ciliary epithelial (NPE) cells facing the aqueous humour. Gap junctions link adjacent cells within and between these layers. Secretion proceeds in three steps: (1) uptake of NaCl from stroma to PE cells by electroneutral transporters, (2) passage of NaCl from PE to NPE cells through gap junctions, and (3) release of Na+ and Cl- through Na+,K+-activated ATPase and Cl- channels, respectively. Most of our understanding of inflow mechanisms has been obtained by studying in vitro preparations at subcellular, cellular and tissue levels. A particularly productive approach has been the electron probe X-ray microanalysis (EPMA) of the elemental composition of excised ciliary epithelium. This technique permits analysis of adjacent cells within different regions of the ciliary epithelium. EPMA of rabbit preparations has supported the idea that paired activity of Na+/H+ and Cl-/HCO3- antiports can be the dominant mechanism underlying the first step in secretion, stromal NaCl uptake by PE cells. EPMA also indicates that Cl- turnover is faster in the anterior than the posterior region of the epithelium. At the opposite epithelial surface, release of Na+ through Na+,K+-activated ATPase of NPE cells is also greater anteriorly than posteriorly. The accompanying release of Cl- through ion channels is enhanced by agonists of A3 adenosine receptors (ARs). The concepts that paired antiport activity is important in stromal NaCl uptake and that A3ARs modulate NaCl release into the aqueous humour were based on in vitro studies. The potential relevance of these conclusions to in vivo conditions has been tested by measurements of IOP in the living mouse. The results have confirmed the predictions that inhibitors of Na+/H+ antiports lower IOP, and that A3AR agonists and antagonists raise and lower IOP, respectively.
眼压（IOP）反映了房水流入和流出之间的平衡。青光眼医学治疗的一个主要策略是减少房水流入，从而降低眼压。因此，了解房水流入的机制和调节具有明确的临床意义。已经确定了许多房水流入的潜在机制。然而，这些机制的整合和调节尚不清楚。房水通过将溶质（主要是氯化钠）从基质转运到眼后房，通过睫状体上皮分泌，水被动跟随。上皮由两层组成：与基质相邻的色素睫状上皮（PE）细胞，以及面向房水的非色素睫状上皮（NPE）细胞。缝隙连接连接这些层内和层间的相邻细胞。分泌过程分三步进行：（1）通过电中性转运体将氯化钠从基质摄取到PE细胞；（2）氯化钠通过缝隙连接从PE细胞进入NPE细胞；（3）分别通过钠钾激活的ATP酶和氯离子通道释放钠离子和氯离子。我们对房水流入机制的大部分理解是通过在亚细胞、细胞和组织水平上研究体外制备物获得的。一种特别有效的方法是对切除的睫状体上皮进行电子探针X射线微分析（EPMA），以分析其元素组成。该技术允许分析睫状体上皮不同区域内的相邻细胞。对兔制备物的EPMA支持了以下观点：钠氢和氯碳酸氢根反向转运体的配对活性可能是分泌第一步（PE细胞摄取基质中的氯化钠）的主要机制。EPMA还表明，上皮前部的氯离子周转率比后部更快。在相对的上皮表面，NPE细胞通过钠钾激活的ATP酶释放钠离子的量也前部比后部更大。通过A3腺苷受体（AR）激动剂，氯离子通过离子通道的伴随释放会增强。配对反向转运体活性在基质氯化钠摄取中很重要以及A3AR调节氯化钠释放到房水中的概念是基于体外研究得出的。通过测量活体小鼠的眼压，已经测试了这些结论与体内情况的潜在相关性。结果证实了以下预测：钠氢反向转运体抑制剂可降低眼压，A３AR激动剂和拮抗剂分别会升高和降低眼压。
