Pathogenesis of proliferative vitreoretinopathy. Modulation of retinal pigment epithelial cell functions by vitreous and macrophages.

RPE cell migration and proliferation are believed to play a role in the pathogenesis of PVR. Since PVR develops in situations where vitreous contacts the RPE, we sought to determine whether human vitreous contains factors that stimulate proliferation and migration of RPE cells. We found that postmortem human vitreous stimulates migration but not proliferation of human RPE cells in vitro under serum-free conditions. A significant vitreous growth factor activity for RPE cells and fibroblasts, however, could be released by admixture of albumin with the vitreous. These findings suggest that vitreous contributes modulators that stimulate some functions of RPE cells that are believed to play a role in the pathogenesis of PVR (fig. 22). Since macrophages are a ubiquitous component of periretinal membranes, we sought to determine whether they modulate proliferation and/or migration of RPE cells, functions that may be essential for the development of PVR. Using an in vitro assay, we found that macrophage supernatant contains factors that stimulate proliferation and migration of cultured human RPE cells. Since IL-1 is a product of activated macrophages that modulates a number of cellular functions, we also examined its effect on RPE proliferation and migration. We found that IL-1 increased migration but did not affect proliferation, and thus could not duplicate the effect of macrophage supernatant. Injection of activated macrophages into the vitreous of rabbits which had a retinal hole stimulated RPE cell proliferation in the area of the retinal hole, where the RPE cells were exposed. These findings suggest the ability of macrophages to modulate functions of RPE cells that are thought to be critical for the development of PVR (fig. 22). We initiated studies to define modulation of cultured RPE cell morphology by exposure to vitreous or to macrophage-conditioned media. Vitreous, serum, and albumin alone had no effect on the epithelial appearance of RPE cells in vitro. However, macrophage-conditioned media and vitreous-serum or vitreous-albumin mixtures induced a reversible fibroblast-like appearance in these cells. These findings show that macrophages produce a morphoplastic substance for RPE cells, and suggest that vitreous also contains a factor(s) that affects RPE cell shape, and that requires mediation by serum components (fig. 22).