“…Water transport is secondary to net ion efflux from the RPE, mainly of K + and Cl − ; other major solutes of the subretinal space that influence water efflux include H + , CO 2 , H 2 CO 3 , HCO 3 − , and lactate. Further, a number of RPE proteins are known or postulated to mediate solute and water transport, such as the apical Na + , K + ATPase, potassium channel KCNJ13 (Kir7.1), Na + -K + -2Cl − cotransporter, and Na + -H + antiporter; basolateral chloride channels CFTR, BEST1, and CLCN2 (ClC-2) and the Cl − -HCO 3 − exchanger SCL4A2 (AE2); apical and basolateral AQP1 (aquaporin), monocarboxylate transporters MCT1 and MCT3, and sodium bicarbonate cotransporters; and intracellular carbonic anhydrase, which converts dissolved CO 2 gas to H 2 CO 3 [1,[6][7][8][9][10]. However, uncertainties remain about the contribution of these specific transporters and channels to RPE ion, solute, and water transport in vivo, which may benefit from studying animal models that disrupt them.…”