CYTOKINE EFFECTS ON PHAGOCYTOSIS OF ROD OUTER SEGMENTS BY RETINAL-PIGMENT EPITHELIAL-CELLS OF NORMAL AND DYSTROPHIC RATS

Purpose. Phagocytosis of rod outer segments (ROS) is an important func tion of retinal pigment epithelial (RPE) cells. Since the details of t he process are not fully known, we studied effects of cytokines produc ed by RPE and photoreceptor cells on phagocytosis of ROS by rat RPE ce lls. Methods. RPE cells were isolated and cultivated from two strains of rats: Sprague-Dawley (SD) rats with normal phagocytosis and Royal C ollege of Surgeons (RCS) rats, which have genetic deficiencies in ROS phagocytosis. A double immunofluorescence staining technique was used to study the effects in vitro of several cytokines on phagocytosis of ROS. Results. We found that transforming growth factor beta-1 (TGF-bet a 1) had dose-dependent effects on RPE cells of both strains of rat: a t a concentration of 10 ng/ml, TGF-beta 1 significantly (p < 0.01) red uced total ROS (to 74% of control in SD rats and to 51% of control in RCS rats), reduced bound ROS (to 56% of control in SD rats and to 48% in RCS rats), and increased the ratio of ingested ROS to total ROS (to 140% in SD rats but not significantly in RCS rats). Treatment of medi um with anti-TGF-beta 1 antibody before incubation of RPE cells of SD rats with TGF-PI decreased the magnitude of these effects. The cytokin e acidic fibroblast growth factor (aFGF 10 ng/ml) affected RPE cells o f SD rats only, decreasing ROS ingested to 56% of control and the rati o of ingested ROS to total ROS to 64% of control. We also examined eff ects of basic fibroblast growth factor and insulin-like growth factor. None of the cytokines tested increased ingestion of ROS by RPE cells of RCS rats. Conclusions. Our results suggest that TGF-beta 1 and aFGF have roles in regulating ROS phagocytosis by normal and dystrophic RP E cells in the rat.