Basis of chloride transport in ciliary epithelium

The aqueous humor is formed by the bilayered ciliary epithelium. The pigmented ciliary epithelium (PE) faces the stroma and the nonpigmented ciliary epithelium (NPE) contacts the aqueous humor. Cl(-) secretion likely limits the rate of aqueous humor formation. Many transport components underlying Cl(-) secretion are known. Cl(-) is taken up from the stroma into PE cells by electroneutral transporters, diffuses to the NPE cells through gap junctions and is released largely through Cl(-) channels. Recent work suggests that significant Cl(-) recycling occurs at both surfaces of the ciliary epithelium, providing the basis for modulation of net secretion. The PE-NPE cell couplet likely forms the fundamental unit of secretion; gap junctions within the PE and NPE cell layers are inadequate to maintain constancy of ionic composition throughout the epithelium under certain conditions. Although many hormones, drugs and signaling cascades are known to have effects, a persuasive model of the regulation of aqueous humor formation has not yet been developed. cAMP likely plays a central role, potentially both enhancing and reducing secretion by actions at both surfaces of the ciliary epithelium. Among other hormone receptors, A(3) adenosine receptors likely alter intraocular pressure by regulating NPE-cell Cl(-) channel activity. Recently, functional evidence for the regional variation in ciliary epithelial secretion has been demonstrated; the physiologic and pathophysiologic implications of this regional variation remain to be addressed.