The Retinal Pigment Epithelium

The RPE forms a pigmented monolayer posterior to the photoreceptors. The RPE forms tight intercellular junctions that create a barrier between the outer retina and the underlying highly vascular and leaky choriocapillaris. The transepithelial resistance of the RPE is of the order of 200-500 Q.cm2, depending upon the species. The outer

From: Ophthalmology Research: Ocular Transporters in Ophthalmic Diseases and Drug Delivery Edited by: J. Tombran-Tmk and C. J. Barnstable © Humana Press, Totowa, NJ

retina depends upon the RPE for survival and the maintenance of visual function. The RPE participates in the transportation of essential amino acids and fatty acids, and is responsible for the isomerization of all-trans-retinal into 11-cis-retinal that is used by the photoreceptors in phototransduction. The RPE also contains, at the apical and basal membranes, numerous ion channels, pumps and co-transporters that regulate pH, fluid transportation and the ionic composition of the subretinal space. For a review of the RPE's physiological roles see Strauss (2005) (1).

The flow of the choroidal circulation is high, owing to the large metabolic demand of the outer retina. Consequently, the basal membrane of the RPE is exposed to a large variety of endogenous and exogenous substances that must be either excluded from, or transported to, the outer retina. Transporters whose function is to transport taurine (2), monocarbocylic acids (3), glucose (4) and folic acid (5) have all been identified in the RPE of different species, as well as RPE cell lines. Associated with the RPE are several drug transporters whose substrates overlap, but serve to protect the RPE and the outer retina from assault from potentially harmful substances. Recent findings have demonstrated a novel organic cation transporter in the apical region of rat RPE cells (6). Furthermore, an organic anion transporter has also been demonstrated to occur in human RPE subcultures (7). The multidrug resistance-associated protein (MRP), which shares some substrates with P-glycoprotein (P-gp), has also been localized to the RPE (8). For a review of ocular drug transporters see Mannermaa et al. (2006) (9).

P-glycoprotein is an efflux pump that confers multidrug resistance (MDR) upon a tissue by actively removing a large range of compounds from the plasma membrane. However, the presence of P-gp can also prevent potentially therapeutic drugs from reaching the outer retina. In particular P-gp confers chemoresistance to tumors with the upregulation of MDR1 transcript (10). In normal tissue, P-gp is expressed in the gut, testes, liver, kidney, adrenal gland, choroid plexus, and brain endothelium forming the blood-brain barrier, which is consistent with P-gp's role as an efflux pump designed to remove xenobiotics (11-14).

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