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Vadivel Ganapathy, Paresh Chothe, Sudha Ananth, J Jwala, A D. Vadlapudi, A K. Mitra, P M. Martin, S B. Smith; Transport Of Oligopeptides In Corneal Epithelial Cells: An Ideal System For Delivery Of Peptides And Peptidomimetic Drugs Into The Anterior Chamber Of Eye. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4195.
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Trans-corneal transfer is a means to deliver drugs into the anterior chamber of eye following topical application. Corneal epithelium expresses a variety of transporters that facilitate trans-corneal transfer of specific drugs based on their structural specificity. The peptide transporters PEPT1 and PEPT2 are expressed in these cells, which transport small peptides consisting of 2 or 3 amino acids. Recently, two new transport systems, SOPT1 and SOPT2, have been identified in mammalian cells, which transport larger peptides consisting of 5 or more amino acids. Here the expression of these oligopeptide transporters in corneal epithelium was investigated.
Expression of SOPT1 and SOPT2 in human and rabbit corneal epithelial cells was evaluated by the uptake of [3H]-Deltorphin (a heptapeptide), a preferred substrate for SOPT1, and [3H]-DADLE (a pentapeptide), a preferred substrate for SOPT2. Trans-corneal transfer of [3H]-DADLE in intact rabbit cornea was monitored in Ussing chamber.
Human corneal epithelial cells possessed robust uptake activity for both Deltorphin (SOPT1) and DADLE (SOPT2). The uptake of Deltorphin was largely Na+-dependent whereas that of DADLE was only partially Na+-dependent. These two uptake processes were additionally distinguishable by the differential effects of di- and tripeptides, which stimulated Deltorphin uptake but inhibited DADLE uptake. In contrast to human corneal epithelial cells, rabbit corneal epithelial cells expressed only SOPT2 with robust uptake activity for DADLE, which was inhibited by di- and tripeptides. Ussing chamber studies with excised rabbit cornea revealed that DADLE transfer occurred with a permeability coefficient that was 6 times greater than that of the passive permeability marker mannitol.
Corneal epithelial cells express the oligopeptide transporters SOPT1 and SOPT2 in a species-dependent manner. These transporters offer an ideal mode of delivery system for peptide and peptidomimetic drugs into the anterior chamber of eye via trans-corneal transfer.
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