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Leena Pitkänen, Veli-Pekka Ranta, Hanna Moilanen, Arto Urtti; Permeability of Retinal Pigment Epithelium: Effects of Permeant Molecular Weight and Lipophilicity. Invest. Ophthalmol. Vis. Sci. 2005;46(2):641-646. doi: 10.1167/iovs.04-1051.
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purpose. To determine the effects of solute molecular weight and lipophilicity on the permeability of a retinal pigment epithelium (RPE)-choroid preparation.
methods. Fresh RPE-choroid specimens from bovine eyes were placed in diffusion chambers for permeability experiments with carboxyfluorescein, fluorescein isothiocyanate (FITC)-labeled dextrans with molecular masses from 4 to 80 kDa, and β-blockers exhibiting a wide range of lipophilicity (atenolol, nadolol, pindolol, timolol, metoprolol, and betaxolol). Permeability experiments were performed both in the choroid-to-retina (inward) direction and in the retina-to-choroid (outward) direction. Carboxyfluorescein and FITC-dextrans were determined by fluorometry, and β-blockers by HPLC. The transepithelial electrical resistance and potential difference were monitored during the experiments.
results. Permeability of the fluorescent FITC-dextran probes through RPE-choroid decreased significantly with the increasing size of the probe. RPE-choroid was 35 times more permeable to carboxyfluorescein (376 Da) than to FITC-dextran 80 kDa. The permeabilities of lipophilic β-blockers were up to 8 and 20 times higher than that of hydrophilic atenolol and carboxyfluorescein, respectively. The lag time of solute flux across the RPE-choroid increased with the molecular weight and lipophilicity. Compared with published data on isolated sclera, bovine RPE-choroid was 10 to 100 times less permeable to hydrophilic compounds and macromolecules. The permeability of lipophilic molecules in RPE-choroid was in the same range as in the sclera.
conclusions. RPE is a major barrier and may be the rate-limiting factor in the retinal delivery of hydrophilic drugs and macromolecules through the transscleral route. For lipophilic molecules, RPE-choroid, and sclera are approximately equal barriers.
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