RETINAL-PIGMENT EPITHELIAL-CELL PROLIFERATION - POTENTIATION BY MONOCYTES AND SERUM

Background: The development of proliferative vitreoretinopathy (PVR) r esults often from a breakdown of the blood-retina barrier and the intr aocular accumulation of serum proteins and leukocytes, particularly mo nocytes, that then come into contact with retinal pigment epithelial ( RPE) cells. To examine the effect of these two factors on RPE prolifer ation, which is characteristic of PVR, we used a coculture system of b lood monocytes and human RPE cells. Methods: RPE cells were incubated with a variable number of monocytes at different serum concentrations and assayed for proliferation by [H-3]-thymidine incorporation and cel l counting. To assess cell-cell communication, RPE cells were labeled with 2',7'-bis(carboxyethyl)-5(and 6) carboxyfluorescein acetoxy-methy l ester, and the dye transfer to monocytes was analyzed using an UV mi croscope. Results: Monocytes (P<0.0004) and serum (P<0.0001), each on its own, significantly stimulated RPE cell growth, and these two varia bles were interrelated (P<0.0001), showing a potentiating synergism. I n serum-free medium, monocytes increased proliferation to just above c ontrol levels, whereas the same number of monocytes in 5% serum increa sed the [H-3]-thymidine incorporation 3.8 times. This effect was great ly reduced by prevention of direct cell contact by means of placement of a well insert, which also lessened the monocyte-induced proliferati on in both serum-free and serum-containing medium. Furthermore, the tr ansfer of the intracellular dye from RPE cells to cocultured monocytes indicates that RPE cells transferred parts of their cytoplasm to mono cytes. Conclusion: These observations underline the importance of prot ein leakage through a damaged blood-ocular barrier and of direct conta ct of monocytes/macrophages with RPE cells, as well as their reciproca l potentiating effect on RPE cell proliferation. Thus, early stabiliza tion of the blood-ocular barrier, which would preclude or reduce prote in leakage and invasion of inflammatory cells into the eye, could be a target for pharmacologic prevention of PVR.