Induction of DNA synthesis by co-culture of retinal glia and pigment epithelium.

Retinal glia (RG) and retinal pigment epithelial cells (RPE) have been previously identified in intravitreal cellular membranes of patients with proliferative vitreoretinopathy (PVR). This study was undertaken to determine if the co-presence of both cell types might lead to increased membrane growth due to some heterotypic cell interactions that enhance cell proliferation. Cell proliferation in co-cultures of RPE plus RG, RPE plus dermal fibroblasts (DF), or RG plus DF was evaluated by quantitation of labeled nuclei in radioautographs prepared from monolayer co-cultures exposed to 3H-thymidine. In each co-culture, one cell type was premarked by phagocytosis of latex particles so that the cells could be identified and the labeling rates in each cell type could be assessed. In co-cultures of RPE and RG, both cell types exhibited a higher labeling rate. In RG-DF co-cultures, DF-labeling was increased, but RG-labeling was unaffected or suppressed. Co-culture of RPE and DF did not affect labeling in either cell type. Studies of conditioned media suggested that RG stimulate RPE and DF by means of a product secreted into the culture medium by the RG. Further, cell-cell contact might modulate the growth response at least for RG. The interaction of RPE and RG in co-culture differed from the interaction of either cell type with DF in that the co-culture of RPE and RG resulted in a higher apparent proliferation rate for both cell types. If similar interactions occur in vivo, the presence of both types of retinal cells in intravitreal membranes of PVR might result in greater growth than in lesions derived from a single retinal cell population.