ACTA-EVER lecture 2007. The retinal pigment epithelium: friend or foe?

The retinal pigment epithelium (RPE) plays an important role in the physiology and pathophysiology of the vertebrate retina. The RPE absorbs fluid from the retinal extracellular space, via a proton-lactate-water co-transport mechanism located in the apical membrane of the epithelium. This mechanism can account for the apparent capability of the RPE to absorb water against an osmotic gradient. RPE cells participate in retinal wound healing. We have created a porcine model of experimental choroidal neovascularization (CNV). In this model, the CNV eventually becomes enveloped by seemingly proliferating RPE cells. By means of 5-bromo-2-deoxyuridine (BrdU) labelling, we studied the proliferation of RPE cells in the porcine eye after experimental posterior pole injury. Surprisingly, we found that only the peripheral RPE cells incorporated the BrdU label, indicating that central injury elicits peripheral RPE proliferation. This might suggest the existence of a peripheral pool of RPE stem cells. RPE cell proliferation plays a role in the pathological wound healing known as proliferative vitreoretinopathy. Antiproliferative agents have been tried to treat this condition but with little success so far. We report on a drug delivery system under development where a prodrug of the antimetabolite 5-fluoro-uracil (5-FU) is suspended in the silicone oil used as a surgical device in the treatment of proliferative vitreoretinopathy (PVR). The theoretical advantage of this approach is that it allows for long contact times between therapeutic, and non-toxic, concentrations of 5-FU and the RPE.