Oxyopia Abstract

February 22, 2002
Noon
489 Minor Hall

Joseph A. Bonanno, OD, PhD
School of Optometry, Indiana University
Host: Sheldon Miller

Title

"Modulation of anion transport in corneal endothelial cells"

Abstract

Through the ion and fluid transport properties of the corneal endothelium, corneal stromal hydration and corneal transparency are maintained. Endothelial function requires HCO3- and is slowed by inhibitors of carbonic anhydrase. As such, my lab has focused on mechanisms for HCO3- transport and intracellular pH regulation. Transendothelial HCO3- flux would require basolateral (stromal side) HCO3- uptake and apical (anterior chamber side) efflux. We have identified and characterized robust basolateral Na+:HCO3- uptake, however the apical efflux mechanisms have been elusive. Recently, we have identified two possible apical efflux mechanisms: 1) CO2 diffusion followed by conversion to HCO3- on the apical surface catalyzed by membrane bound carbonic anhydrase and 2) apical anion channels. The cystic fibrosis transmembrane conductance regulator (CFTR) is located on the apical membrane. Stimulating CFTR (Adenosine, forskolin, genistein) increases apical Cl- and HCO3- permeability. Purinergic agonists (ATP) also increase apical Cl- and HCO3- permeability, possibly via Calcium activated Cl- channels (CaCC). Thus in the absence of exogenous agents, cellular ATP release and its conversion to adenosine at the surface may contribute to baseline anion flux and fluid transport. Further, we have found that HCO3- itself can increase cellular [cAMP] (through the action of soluble adenylyl cyclase), phosphorylate CFTR and increase apical Cl- permeability. We suggest that robust endothelial cell HCO3- uptake not only plays a role as a transport component, but also contributes to maintaining [cAMP] and thereby enhances apical anion permeability.

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