HUMAN RETINAL-PIGMENT EPITHELIUM IN-VITRO - INFLUENCE OF LOW-OXYGEN TENSION, GLUCOSE AND INSULIN

Retinal pigment epithelium (RPE) cells migrating through the damaged r etina into the vitreous body seem to play an important role for the pa thogenesis of proliferative vitreoretinopathy (PVR) and other prolifer ative retina diseases. It is so far not known how the RPE cells are ab le to survive in the vitreous body without contact to the blood vessel s of the choroid supplying them with oxygen and nutritive substances. To answer this question, we studied growth characteristics and sensiti vity to glucose and insulin of human RPE cells, incubated with reduced oxygen partial pressure. In the first study, RPE cultures of 58 postm ortem human eyes were grown with 5% O2/5% CO2 and with standard condit ions (20% O2/5% CO2). The growth was assessed in five graded stages. O ur data show that human RPE grows better under 5% oxygen than under 20 % O2 (P < 0.0001). In consideration of this effect, we cultivated, in a further study, pigment epithelium of 49 postmortem human eyes with 5 % oxygen and with 4 different glucose concentrations with and without addition of insulin. We found that glucose in higher concentrations w as a potent stimulator of growth, whereas insulin was a modest stimula tor when used alone. The combination of glucose and insulin was signif icantly more effective (p = 0.01) in the period of the first 7 days. T hese results suggest that proliferation of human RPE cells can be incr eased by oxygen reduction, glucose and insulin. These interactions may help in understanding the pathophysiology of retina damage and prolif erative retina diseases like PVR.