Abstract
BackgroundThe proliferation of retinal pigment epithelium (RPE) cells resulting from an epithelial-mesenchymal transition (EMT) plays a key role in proliferative vitreoretinopathy (PVR), which leads to complex retinal detachment and the loss of vision. Genes of Snail family encode the zinc finger transcription factors that have been reported to be essential in EMT during embryonic development and cancer metastasis. However, the function of Snail in RPE cells undergoing EMT is largely unknown.Principal FindingsTransforming growth factor beta(TGF-β)-1 resulted in EMT in human RPE cells (ARPE-19), which was characterized by the expected decrease in E-cadherin and Zona occludin-1(ZO-1) expression, and the increase in fibronectin and α-smooth muscle actin (α-SMA) expression, as well as the associated increase of Snail expression at both mRNA and protein levels. Furthermore, TGF-β1 treatment caused a significant change in ARPE-19 cells morphology, with transition from a typical epithelial morphology to mesenchymal spindle-shaped. More interestingly, Snail silencing significantly attenuated TGF-β1-induced EMT in ARPE-19 cells by decreasing the mesenchymal markers fibronectin and a-SMA and increasing the epithelial marker E-cadherin and ZO-1. Snail knockdown could effectively suppress ARPE-19 cell migration. Finally, Snail was activated in epiretinal membranes from PVR patients. Taken together, Snail plays very important roles in TGF-β-1-induced EMT in human RPE cells and may contribute to the development of PVR.SignificanceSnail transcription factor plays a critical role in TGF-β1-induced EMT in human RPE cells, which provides deep insight into the pathogenesis of human PVR disease. The specific inhibition of Snail may provide a new approach to treat and prevent PVR.
Highlights
Proliferative vitreoretinopathy (PVR), a scarring process that develops with some retinal detachments (RDs), is the most common cause of surgical failure in the rhegmatogenous RD treatment [1]
Epithelial to mesenchymal transition is an essential morphological conversion occurring during embryonic development, and this process is re-engaged in adults during wound healing, tumor progression and organ fibrosis [20]
retinal pigment epithelium (RPE) cells are the major cell type involved in the pathogenesis of proliferative vitreoretinopathy (PVR), which results from the epithelial-mesenchymal transition (EMT), proliferation, and migration of transformed RPE cells to the vitreous[5,21,22]
Summary
Proliferative vitreoretinopathy (PVR), a scarring process that develops with some retinal detachments (RDs), is the most common cause of surgical failure in the rhegmatogenous RD treatment [1]. PVR is a dynamic process which is characterized by the formation of fibrotic tissue both on the detached retina. The retinal pigment epithelium (RPE) cells are main contributor to the development of fibrotic tissue on the retina. With the development of retinal break and detachment and alteration of the Blood-retina Barrier, RPE cells are exposed to a variety of cytokines, growth factors containing in serum. RPE cells undergo epithelial-mesenchymal transition (EMT) and form fibroblast-like cells, and produce extracellular matrix components participating in the fibrotic tissue formation on the detached retina [5]. The proliferation of retinal pigment epithelium (RPE) cells resulting from an epithelial-mesenchymal transition (EMT) plays a key role in proliferative vitreoretinopathy (PVR), which leads to complex retinal detachment and the loss of vision. The function of Snail in RPE cells undergoing EMT is largely unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
