To our knowledge, the functional characteristics of the RPE tight junction have not been described. Like many epithelia, the RPE is cation selective, but this selectivity appears to be due to the permeability of K
+ rather than that of Na
+. Claudins determine ion selectivity by mechanisms still under investigation.
17 The only claudins known to be associated with native or high-functioning RPE junctions were claudin-10 and -19.
22,39,41 Mutations in claudin-19 are associated with renal disease and visual impairment. In the kidney, claudin-19 forms a complex with claudin-16 and decreases the permeability to Cl
−. Claudin-16 increases the permeability to Na
+, which further increases cation selectivity.
52 We found that RPE lacked claudin-16, which raises the question of how claudin-19 functions in the RPE. Other claudins known to affect Na
+ and K
+ permeability are claudin-2, which also increases Na
+ permeability,
53 and claudin-9, which decreases K
+ permeability.
54 The expression of these claudins by hfRPE remains an open question until we can resolve the uncertainty about the antibodies and the variability of claudin-2 expression mentioned earlier. The presence of claudin-10 could increase selectivity for cations in the regions where it is expressed.
55 On the other side of the equation, RPE lacked claudin-4 and -7, which increase Cl
− permeability.
53 Those authors found that claudin-3 had no effect on Na
+/Cl
− selectivity, but the effect on K
+ was not examined. Taken together, we found claudins that are consistent with the known physiology that predicts a cation-selective junction. RPE expresses claudins that would preferentially decrease permeability to Cl
−, but lacks claudins that would increase permeability to Na
+. The reason for the relatively high K
+ permeability requires further investigation, but the data conform to a higher-order Eisenman sequence for cation selectivity.
35 The study of ion selectivity reported herein defines a baseline for explorations of how individual claudins fine-tune selectivity by manipulating claudin expression.