Cornea paracellular transport

There is growing evidence implicating Na+-dependent solute transporters and intracellular as well as extracellular Ca2+ in the physiological regulation of the paracellular pathway [81,203,204], Such modulation of paracellular permeability is especially important for drugs such as peptides and oligonucleotides that exhibit poor permeability characteristics across both the cornea and the conjunctiva [150,152,154,155], In addition, ion transporters such as Cl and Ca2+ channels have been implicated in macromolecular transport (see Sections IV.B.2 and IV.B.4). In the following discussion, some key ion transport processes and their possible roles in solute transport across epithelial tissues are summarized. 

The effects of D-glucose observed in vivo are not well reproduced in vitro. Madara [203] reported that cytoskeletal contraction and enhanced paracellular permeability were observed only in an in situ perfusion preparation and not in an isolated tissue preparation. Although its in vivo effect was not tested, 25 mM D-glucose, an effective concentration in the jejunum [47], failed to enhance the in vitro transport of sotalol (log PC = -0.62), atenolol (log PC = 0.16), or nadolol (log PC = 0.93) across the isolated conjunctiva [213], For a similar reason and possibly due to the absence of a Na+-glucose cotransporter in the cornea, 25 mM D-glucose was ineffective in increasing the corneal transport of these three drugs. 

Modulation of CL channels is expected to alter paracellular drug transport across the cornea and the conjunctiva by modulating either net water transport or intracellular levels of Ca2+. In general, epithelia with CL channels secrete CL along... 

UB Kompella, P Ashton, VHL Lee. (1992). Paracellular drug transport in the pigmented rabbit conjunctiva and cornea. Invest Ophthalmol Vis Sci 33 1015. 

For most topically applied drugs, passive diffusion along the concentration gradient, either transcellularly or paracellularly, is the main permeation mechanism across the cornea. Occasionally, a carrier-mediated active transport mechanism is indicated (Liaw et al. 1992). Lipophilic drugs tend to favour the transcellular route, whereas hydrophilic drugs usually permeate via the paracellular route through intercellular spaces (Borchardt 1990). 

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