Does the circadian clock make RPE-mediated ion transport “tick” via <i>SLC12A2</i> (NKCC1)?

The presence of a circadian clock in the retinal pigment epithelium (RPE) was discovered recently. However, little is known about mechanisms or processes regulated by the RPE clock. We cultured ARPE-19 monolayers in a transwell culture system, and we found rhythmic mRNA expression of the sodium-potassium-chloride co-transporter <i>SLC12A2</i>. We localized the corresponding protein product, NKCC1, on the apical membrane of ARPE-19 cells. We found that concentrations of sodium, potassium, and chloride oscillated in apical supernatants. The ion concentration gradients between supernatants strongly correlated with <i>SLC12A2</i> mRNA expression. Our results suggest that the circadian clock regulates ion transport by the RPE via NKCC1 expression.