The retinal pigment epithelium (RPE) is a monolayer of cuboidal cells
that lies in close association with the rod and cone photoreceptors. T
his epithelium has diverse features, three of which are discussed in s
ome detail in this review, namely the daily phagocytosis of rod and co
ne outer segment fragments that are shed from their distal ends; the u
ptake, processing, transport and release of vitamin A (retinol) and so
me of its visual cycle intermediates (retinoids); and some of the aspe
cts of its apical and basolateral membrane polarity that are the rever
se of most other epithelia. Phagocytosis takes place at the apical sur
face via membrane receptor-mediated processes that are not yet well de
fined. Retinol uptake occurs at both the basolateral and apical surfac
es by what appear to be separate receptor-mediated processes. The rele
ase of a crucial retinoid, 11-cis retinaldehyde (11-cis retinal), occu
rs solely across the apical membrane. Delivery of retinol across the b
asolateral membrane is mediated by a retinol binding protein (RBP) tha
t is secreted by the liver as a complex with retinol (vitamin A). With
in the cell, retinol and its derivatives are solubilized by intracellu
lar retinoid binding proteins that are selective for retinol (cellular
retinol binding protein, CRBP) and 11-cis retinoids (cellular retinal
binding protein, CRALBP). Release of 11-cis retinal across the apical
membrane and re-uptake of retinol from the photoreceptors during the
visual cycle is promoted by an intercellular retinoid binding protein
(IRBP). Na,K-ATPase, the membrane-integrated enzyme required to set up
the ion gradients that drive other ion transporters, is largely local
ized to the apical membrane. This is the reverse of most epithelia. Th
e RPE expresses the enveloped viral G protein and hemagglutinin on its
basolateral and apical surface, respectively and does not appear to p
ossess a general scheme for reversal of memrane protein polarity. Ther
efore possible alternative mechanisms for this reversal in Na,K-ATPase
polarity are discussed. They include unique domains in the primary am
ino acid sequence of Na,K-ATPase subunits, cytoskeletal elements and c
omponents of the extracellular matrix. The precise mechanism remains u
nresolved.