Retinal Pigment Epithelium

RPE is a monolayer of hexagonal cells separating the outer surface of the neural retina from the choriocapillaries. Many of these cells are multinu-

cleated, and the nuclei are located in the basal portion of the cell. RPE plays a central role in regulating the microenvironment surrounding the photoreceptors in the distal retina, where the phototransduction takes place. The outer segments of rods and cones are closely associated with the RPE via villous and pesudopodial attachments. The RPE phagocytoses distal potions of rod and cone outer segments.

Following intravitreal injection, horseradish peroxidase crosses the inner limiting membrane, ganglion cell layer, inner plexiform layer (synaptic layer), inner nuclear membrane, outer limiting membrane, and the layer of the photoreceptors but blocked by the tight junctions of the retinal pigment epithelial cells (Tornquist et al., 1990). Thus, the retinal pigment epithelium is a principal barrier to solute transport. Macromolecules such as horseradish peroxidase that escape from the permeable vessels of the chorioca-pillaries, cross Bruch's membrane and penetrate the intercellular clefts of the retinal pigment epithelium. Further progression into the retina is blocked by the junctional complexes of the RPE (Tornquist et al., 1990). In a number of vertebrate species, these junctional complexes consist of zonula occludens, zonula adherens, and gap junctions, and their surface specializations are different from those observed in other epithelia (Hudspeth and Yee, 1973). The gap junctions lie apically (vitread), the zonula adherens lie basally (sclerad), and the zonula occludens overlap the other two junctions. With the presence of tight junctions, RPE forms a polarized monolayer of cells with morphologically and functionally distinct apical and basolateral membranes. The apical membrane of RPE faces the photoreceptor outer segment across the subretinal space, and the basolateral membrane is juxtaposed to the choriocapillaries across Bruch's membrane. Various transporter proteins are distributed in a polarized manner in RPE (Rodriguez-Boulan and Nelson, 1989; Mays et al., 1994).

RPE is extremely restrictive for paracellular transport of solutes due to the presence of tight junctions. However, it is capable of a variety of specialized transport processes (Betz and Goldstein, 1980). To understand the barrier properties of RPE, experimental models such as isolated RPE-chor-oid preparations (Crosson and Pautler, 1982; Tsuboi and Pederson, 1988; Joseph and Miller, 1991; Quinn and Miller, 1992; la Cour et al., 1994), neural retina-RPE-choroid preparations (Shirao and Steinberg, 1987), and confluent monolayers of cultured RPE (Defoe et al., 1994; Hernandez et al., 1995; Gallemore et al., 1995) can be used. The electrical resistance of various RPE and choroid preparations is summarized in Table 1. The electrical resistance of RPE preparations ranges from 70 to 350 ohm-cm2 in various species and preparations. The low in vitro resistance of these preparations does not appear to be representative of the formidable in vivo blood-retinal barrier.

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