POTENTIAL CONTRIBUTION OF EPITHELIAL NA-HUMOR( CHANNEL TO NET SECRETION OF AQUEOUS)

The aqueous humor of the eye is secreted by the bilayered ciliary epit helium, consisting of the pigmented (PE) cell layer facing the stroma and the nonpigmented (NPE) cell layer facing the aqueous humor. Cells within each layer and between the two layers are linked by gap junctio ns, forming a ciliary epithelial syncytium. Unidirectional secretion f rom the stroma to the aqueous proceeds both through the cells (the tra nscellular pathway) and between the cells (the paracellular pathway). Net formation of aqueous humor must, however, be the algebraic sum of unidirectional secretion and unidirectional reabsorption from the aque ous humor back into the stoma. The mechanisms potentially underlying r eabsorption of aqueous humor by the NPE cells have recently been addre ssed by studying the regulatory response (RVI) of anisosmotically shru nken NPE cells. The results indicated that epithelial Na+ channels wit h a high affinity to amiloride likely contribute to reabsorption of so lute from the aqueous humor. We have substantiated this possibility by using Northern analysis to identify in human ciliary body RNA a 3.7-k b transcript corresponding to the alpha-subunit of the amiloride-sensi tive, alpha beta gamma-ENaC epithelial sodium channel, We have also fo und that the Na+-channel inhibitor benzamil inhibits the RVI without a ffecting the cell volume of isotonic cell suspensions. This observatio n supports the hypothesis that the low conductance, highly selective e pithelial Na+ channel is activated by shrinkage and contributes to uni directional reabsorption as aqueous humor. Examples are provided of ho w the integrative regulation of aqueous humor formation can involve co njugate actions on both unidirectional secretion and reabsorption. (C) 1997 Wiley-Liss, Inc.