Modulation of corneal endothelial hydration control mechanisms by Rolipram

Corneal stromal hydration is maintained by an active HCO3- transport mechan ism located in the corneal endothelium. Whilst modulation of transport acti vity by changes in intracellular cAMP concentration have been noted, the si te of effect is undefined. To resolve this question, the effects of Rolipra m, a cAMP phosphodiesterase inhibitor, on endothelial physiology were deter mined. Addition of 0.1 mM Rolipram caused a threefold increase in intracell ular cAMP with no change in cGMP. Associated with the increase in cAMP was a transient whole corneal thinning and a similarly transient increase in tr ans-endothelial potential difference, short-circuit current and resistance. The membrane potential hyper-polarized and the intracellular Na+ concentra tion decreased. The decreased intracellular Na+ was associated with an incr eased rate of Na+ extrusion between the endothelial cell and extracellular space. It is concluded that Rolipram increases the concentration of cAMP wh ich activates the basolateral membrane Na+/K+-ATPase activity and increases net HCO3- transport. In addition there is a reduction in endothelial perme ability which combined with the increase in pump activity may jointly expla in the observed stromal thinning. The duplicity of responses indicates that if cAMP has a physiological role in regulating corneal hydration then it m ay operate on both the endothelial pump and the endothelial permeability.