OXYGEN MODULATES THE RESPONSE OF THE RETINAL-PIGMENT EPITHELIUM TO BASIC FIBROBLAST GROWTH-FACTOR AND EPIDERMAL GROWTH-FACTOR BY RECEPTOR REGULATION

Purpose. To determine if low oxygen affects growth factor responsivene ss in retinal pigment epithelial (RPE) cells and if such effects are m ediated through changes in cell surface receptors. Methods. Proliferat ing human RPE cells were exposed to varying concentrations of exogenou s basic fibroblast growth factor (bFGF) or epidermal growth factor (EG F) at different media oxygen tensions (16 to 147 mm Hg) and cell count s determined after 4 days. Receptor expression was determined by affin ity cross-linking and saturation binding studies on confluent RPE cult ures exposed to varying media oxygen tensions for 2 days. Results. Ret inal pigment epithelial cells exhibited a greater proliferative respon se to exogenous growth factors at hypoxia than at higher media oxygen tensions, and they expressed bFGF and EGF receptors, which were upregu lated under reduced oxygen tensions. Scatchard analysis demonstrated t hat hypoxia caused both an increase in the number of EGF receptors per cell and a shift from low to high affinity receptors. Conclusions. Th ese results suggest that hypoxia not only can stimulate RPE cell proli feration per se, it also can ''prime'' cells to respond more markedly to exogenous growth factors. These observations may be important in el ucidating the cause of proliferative vitreoretinopathy.