Human corneal endothelial cells (HCECs) form a monolayer of hexagonal cells at the back of the cornea and have a pivotal role in regulating corneal stromal transparency. They are notorious for their limited regenerative capacity in vivo – a characteristic that is caused by contact-induced mitotic arrest. On page , Scheffer Tseng and colleagues report that activating p120-catenin trafficking to the nucleus unlocks this block. They show that the conventional approach taken to achieve HCEC expansion, namely disrupting contact inhibition by treatment with EDTA and basic fibroblast growth factor, activates canonical Wnt signalling and induces endothelial–mesenchymal transition (EMT), especially when transforming growth factor β1 (TGF-β1) is present. By contrast, treatment of HCECs with p120-catenin siRNA promotes HCEC proliferation without inducing EMT. This RNAi activates p120-catenin trafficking to the nucleus, which relieves the repressor activity of the transcription factor Kaiso, activates RhoA–ROCK signalling, and inhibits Hippo signalling without activating canonical Wnt signalling. As a result, the cells proliferate without losing their hexagonal shape or their adherens junctions. This new strategy for unlocking the mitotic block of contact-inhibited HCECs could lead to therapies for corneal blinding diseases that are caused by endothelial dysfunction.
