Hyperglycemia and insulin treatment promote the proliferation of retinal pigment epithelium cells in early diabetes: an in vitro and in vivo study

The retinal pigment epithelium (RPE) is associated with the emergence and development of diabetic retinopathy. Interestingly, a previous clinical study observed that the atrophy of RPE cells surrounding the optic disc in type 1 diabetic children were significantly less pronounced compared to normal children, contradicting current reports. In order to explore the molecular mechanisms behind this contradictory phenomenon, we conducted a series of experiments and reached the following results. First, RPE cells proliferation increased in a glucose concentration-dependent manner in vitro, accompanied by elevated Brachyury and CTGF protein expression, but decreased overall cell viability. Secondly, in vitro experiments and diabetes mouse models confirmed that insulin promoted RPE cell proliferation in high glucose concentrations by activating ERK1/2 phosphorylation. Furthermore, insulin down-regulated the expression of Brachyury and CTGF proteins, possibly reducing high-glucose-induced damage to RPE cells. In conclusion, the effect of insulin treatment on the proliferation of RPE cells was significantly more significant than that of hyperglycemia, which may be related to the activation of Erk1/2 or reduction of RPE cell damage by inhibiting the occurrence of EMT.