High glucose concentrations inhibit protein synthesis in retinal pigment epithelium in vitro

There is mounting evidence suggesting functional and structural alterations in the retinal pigment epithelium (RPE) in experimental and clinical diabetes. In this study we examined the effect of high glucose concentrations on human RPE cells in vitro. After 24-hr incubation in media supplemented with glucose (19.5 mM, 25.5 mM, and 45.5 mM) and prepared both with and without osmotic adjustment, there was no significant effect on [3H]thymidine or [3H]uridine incorporation into TCA-precipitable material. There was, however, a significant decrease in [35S]methionine incorporation which became more marked with increasing glucose concentrations. This could not be attributed to increased osmolarity caused by the additional glucose as it occurred in isosmolar high glucose media. 3-O-methyl glucose, a non-metabolized glucose analog, did not have the same effect, suggesting that metabolism of glucose may be important. Resolution of newly synthesized proteins by gel electrophoresis and autoradiography suggests a generalized decrease in protein synthesis. These data suggest that elevated glucose levels cause a significant metabolic alteration in RPE cells in vitro.