[Stimulation of corneal endothelial cell proliferation by interleukins, complete mitogens and corneal parenchymal...

The effects of various cytokines and mitogens on proliferation of rabbit corneal endothelial cells were examined in a serum-free culture. Complete mitogens such as epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and hepatocyte growth factor (HGF) stimulated proliferation of corneal endothelial cells 1.5 to 2 times the control. The effect was dose-dependent up to 10 ng/ml and flattened out at higher concentrations. Interleukins (IL-x) such as IL-1 alpha, IL-1 beta, IL-2, IL-3 or IL-4 by themselves had little or no stimulatory effect on cell proliferation. The combination of IL-1 beta and EGF, or IL-1 beta and TGF-alpha, however, showed a 5- to 6-fold stimulation over the control. IL-1 beta, thus, can be regarded as a co-mitogen that can amplify the stimulatory effect of complete mitogens (EGF and TGF-alpha). The number of corneal endothelial cells increased to 200% when corneal endothelial cells were co-cultured with corneal parenchymal cells. Addition of conditioned medium obtained from the culture of corneal parenchymal cells also increased the number of corneal endothelial cells more than 2-fold. These results suggest that factors which stimulate cell proliferation of corneal endothelial cells are secreted by corneal parenchymal cells.