The primary function of the double-layered ciliary epithelium, comprising pigmented and nonpigmented layers, is the secretion of aqueous humor,
22 which is essential for the maintenance of intraocular pressure and the provision of nutrients to avascular structures of the eye. The driving force for aqueous humor secretion is provided by transepithelial ion transport of Na
+, Cl
− and HCO
3 − generating an osmotic gradient for water movement.
22,60 Ion uptake by the PE cells is followed by diffusion of ions from PE to NPE cells through gap junctions, and ion release from the NPE cells into the posterior chamber.
61 In the present study, we immunolocalized β-ENaC primarily to the opposed apical membranes of PE and NPE layers of ciliary processes and, to a lesser extent, to the basal cell membranes of the PE facing the ciliary stroma. In contrast, γ-ENaC was present primarily along the basal membrane domains of the PE. As discussed, the functional relevance of this incongruent localization of both subunits is not yet clear. However, expression of the α-ENaC subunit in combination with either the β- or the γ-subunit is sufficient to generate a significant sodium flux.
48,62 Thus, strict cellular colocalization of the β- and γ-subunits is not required for relevant channel function provided that α-ENaC is present. In the ciliary epithelium this is likely to be the case, as suggested by our finding that α-ENaC transcripts are abundantly expressed in the ciliary body. Previous studies also have found ENaC expression in ciliary epithelium, consistent with our findings.
26,32,34,35 It has been speculated that ENaC may support reabsorption of Na
+ from the aqueous humor back into the NPE cells.
26 Alternatively, ENaC may facilitate Na
+ uptake from PE cells by the apical membrane of NPE cells which is then secreted by the Na
+/K
+-ATPase at the basolateral membrane facing the aqueous humor. From our immunocytochemical studies we cannot deduce whether ENaC is localized in the apical membrane of NPE or PE cells or both. ENaC expression in the apical membrane of PE cells would be difficult to reconcile with a role of ENaC in aqueous humor secretion. In contrast, the apparent expression of ENaC along the basal membrane domains of PE cells may indicate a role of ENaC in Na
+ uptake into PE cells. However, with our present data we are not yet in a position to propose a coherent model for the role of ENaC in aqueous humor secretion.