The fall and rise of active chloride transport: Implications for regulation of intraocular pressure
Article first published online: 29 OCT 2003
© 2003 Wiley-Liss, Inc.
Journal of Experimental Zoology Part A: Comparative Experimental Biology
Volume 300A, Issue 1, pages 5–13, 1 November 2003
How to Cite
Civan, M. M. (2003), The fall and rise of active chloride transport: Implications for regulation of intraocular pressure. J. Exp. Zool., 300A: 5–13. doi: 10.1002/jez.a.10303
- Issue published online: 29 OCT 2003
- Article first published online: 29 OCT 2003
- National Institutes of Health. Grant Numbers: EY08343, EY013624, EY01583
Early study of transepithelial salt transfer focused on Cl− and not Na+, partly because Cl− was readily measureable. The advent of flame photometry and tracer techniques brought Na+ to the fore, especially since short-circuited frog skin (Rana temporaria) produces baseline net movement of Na+ and not of Cl−. Zadunaisky was among the first to describe what is currently termed secondary active Cl− transport, helping stimulate interest in Cl− handling by other tissues, notably the thick ascending limb of the loop of Henle important in renal counter-current multiplication. More recently, molecules responsible for electroneutral and electrogenic Cl− transfer have been cloned, and specific diseases resulting from their faulty expression have been identified. The clinical importance of transepithelial Cl− transfer is illustrated by studies of aqueous humor formation by the eye's bilayered ciliary epithelium. NaCl is taken up from the stroma by the pigmented ciliary epithelial (PE) layer, diffuses through gap junctions into the nonpigmented ciliary epithelial (NPE) layer, and is released into the aqueous humor largely through Na+ pumps and Cl− channels. ATP released by NPE cells can be ecto-enzymatically metabolized to adenosine. Adenosine can mediate paracrine/autocrine stimulation of Cl− channels and aqueous humor secretion by occupying A3 adenosine receptors (ARs). A3AR agonists indeed elevate, and A3AR antagonists lower, intraocular pressure (IOP) in wild-type mice. A3AR knockout mice have low IOP and their responses to A3AR agonists and antagonists are blunted; this suggests that reducing Cl−-channel activity with A3AR antagonists may provide a novel approach for treating glaucoma. J. Exp. Zool. 300A:5–13, 2003. © 2003 Wiley-Liss, Inc.