Transport mechanisms of the cornea: characterization of barrier permselectivity

Corneal permselectivity was investigated in vitro by measurement of membrane electrokinetic potentials generated either by ionic concentration gradient (diffusion potential) or hydrostatic pressure gradient (streaming potential). Studies on the effect of pH on these potentials indicates dual-selective character to passage of ions across the cornea. The magnitude and polarity of the selectivity are controlled by the degree of protonation of ionizable sites within the cornea. The cornea presents an isoelectric point (pI) of 3.2. At physiological pH and pH above pI, the cornea behaves as if it is negatively charged and allows preferential passage of positive ions with respect to negative ions. Below pI, the reverse is valid. Lowering the ionic strength of the bathing solutions results in an increase in membrane ionic discrimination as well as membrane electrical resistance. Tissue viability and integrity, the two important membrane properties involved in the overall transport process, were investigated. The mechanisms and the significance of membrane pennselectivity to epithelial drug transport are discussed.