Utilizing cultured human and monkey retinal pigment epithelium (RPE), we are assessing at the cellular level what may be the earliest pathological changes in diabetic complications. Cultured RPE may be useful because these cells possess aldose reductase and generate intracellular polyol when insulted with elevated concentrations of hexose sugars, especially galactose, in their media. We have determined that taurine transport into and out of cultured RPE is impaired after cells are incubated with galactose and that this effect is preventable by including aldose reductase inhibitors (ARI) in the galactose-containing medium. In these experiments, we showed that taurine uptake and efflux from RPE cells in vitro could be modulated by changes in the electrochemical gradient for sodium across the cell membrane. When cells were depolarized while the intracellular sodium concentration was abnormally high or when the cells were depolarized in media containing high potassium, there was concomitant loss of taurine or reduced uptake of taurine. We have begun to extend these studies of the effects of changes in membrane potential to the purine nucleotide status of the cells. RPE cells resemble glial cells in that adenosine is released from cells under depolarizing conditions. Since adenosine is a neuromodulator, transient or sustained changes in membrane potential of RPE cells, such as may occur in diabetes, may affect other retinal cells, notably photoreceptors, by means of abnormal release of adenosine and related compounds.
