POLARITY AND THE DEVELOPMENT OF THE OUTER BLOOD-RETINAL BARRIER

The retinal pigment epithelium (RPE) is a monolayer that separates the outer surface of the neural retina from the choriocapillaris. Because the choriocapillaris is fenestrated, it is the RPE that forms the out er blood-retinal barrier and regulates the environment of the outer re tina. Like all epithelia and endothelia, the ability of RPE to regulat e transepithelial transport depends upon two properties: apical tight junctions to retard diffusion through the paracellular spaces of the m onolayer, and an asymmetric distribution of proteins to regulate vecto rial transport across the monolayer. During development, these propert ies form gradually. Initially, the tight junctions are leaky, and the RPE exhibits only partial polarity. As the neural retina and choriocap illaris develop, there are progressive changes in the composition of t he apical junctional complexes, the expression of cell adhesion protei ns, and the distribution of membrane and cytoskeletal proteins. Develo pment can be used to dissect the multiple mechanisms that establish an d maintain polarity and barrier function. These mechanisms are regulat ed by the interactions that develop between the RPE and its neighborin g tissues. This review discusses the remodeling of the apical, lateral and basal plasma membranes of RPE that occurs during normal developme nt, and establishes a framework to integrate the data obtained from mu ltiple species. It examines the progress in understanding how environm ental interactions regulate this development.