RESUMO
Retinal pigment epithelium (RPE) regulates drug transfer between posterior eye segment and blood circulation, but there is no established RPE cell model for drug delivery studies. We evaluated ARPE-19 filter culture model for this purpose. Passive permeability of 6-carboxyfluorescein, betaxolol and FITC-dextran (40kDa) and active transport of 6-carboxyfluorescein, sodium fluorescein, rhodamine 123, cyclosporine A and digoxin in ARPE-19 model were investigated and compared with isolated bovine RPE-choroid tissue. In addition, barrier properties, and mRNA expression of RPE-specific and melanogenesis-related genes (RPE65, VMD2, CRALBP, OTX-2, MITF-A, TRP-1, tyrosinase) were measured in various culture conditions. The filter grown ARPE-19 cell model showed reasonable barrier properties (TER close to 100Omegacm(2)), but its permeability was slightly higher than that of isolated bovine RPE/choroid specimens. In active transport studies the ARPE-19 model mimics qualitatively the permeability profile of bovine RPE-choroid, but ARPE-19 model underestimates the importance of active transport relative to passive diffusion. Long-term filter-cultured ARPE-19 cells expressed various RPE-specific and melanogenesis-related genes at higher levels than the ARPE-19 cells cultured short-term in flasks. ARPE-19 model can be used to study drug permeation processes in the RPE.
