Contraction of extracellular matrix by transdifferentiated retinal pigment epithelial cells, inducers and inhibitors

Abstract

Transdifferentiated retinal pigment epithelial cells (RPE) display enhanced contractile potentials and have been implicated in the development of tractional retinal detachment. This study determines the activity of contraction-promoting factors, examines some involved mechanisms and evaluates inhibitors. Using an in vitro contraction assay, we demonstrated that collagen matrix contraction by transdifferentiated RPE cells is effectively stimulated by serum, platelet-derived growth factor and insulin-like growth factor-1. Endothelin-1 and transforming growth factor-beta 1 and -beta 2 have a more discrete or marginal effect. Tractional forces promoted by these peptides are completely protein synthesis dependent. Contraction stimulated by serum is only partly dependent on de novo protein synthesis, suggesting different active factors and/or pathways. Staurosporine, a broad-spectrum kinase inhibitor, effectively inhibited collagen matrix contraction by transdifferentiated RPE cells regardless of the promoter.