Identity and regulation of ion transport mechanisms in the corneal endothelium

Corneal transparency is dependent on regulation of the hydration of the corneal stroma. Water is driven into the cornea across the epithelial and endothelial cell layers by the stromal swelling pressure. This fluid leak into the cornea is counterbalanced by the corneal fluid pump, which is predominantly attributed to the ion and fluid transport capacity of the endothelial cell layer. Primary and secondary active transport mechanisms are responsible for generating a net ion flux from the stromal to anterior chamber side of the endothelium; however, the identity and location of all the components of this transport system are not known. The endothelial fluid pump is dependent on the presence of Cl- and HCO3-, and can be slowed by carbonic anhydrase inhibitors. A number of anion transport mechanisms have been identified and characterized in the endothelium, including basolateral Na+/2HCO(3)(-) cotransport, Na+/K+/2Cl(-) cotransport, Cl-/HCO3- exchange, and apical anion channels permeable to both Cl- and HCO3-. Furthermore, there is evidence for a carbonic anhydrase mediated CO2-diffusive mode of apical HCO3- flux. These findings are incorporated into a new model of transendothelial anion transport, which suggests that there are a number of alternate pathways for anion transport. There have been few studies on activation of signal transduction pathways that could stimulate endothelial fluid transport. Interestingly, recent studies show that multiple autocrine signaling pathways are in place that could be upregulated during physical stimulation and may be responsible for maintaining basal levels of fluid secretion. (C) 2003 Elsevier Science Ltd. All rights reserved.