Background: The epithelial to mesenchymal transition (EMT) of retinal
pigment epithelial (RPE) cells is a critical event in the pathogenesis of
proliferative vitreoretinopathy and neovascular age-related macular degeneration,
which are the leading causes of severe vision loss. Endoplasmic reticulum (ER)
stress has been implicated in the EMT of many cell types and various ocular
diseases. However, the relationship between ER stress and EMT in RPE cells
remains unknown. Therefore, in the study, we explored the impact of ER stress on
EMT in RPE cells. Methods: Different concentrations of tunicamycin (TM)
and thapsigargin (TG) were used to induce ER stress in human RPE cells. The
expression of epithelial marker, mesenchymal markers and some of genes/proteins
involved in TGF-/Smad signaling were analized by qPCR, western blot or
immunostaining at the condition with or without stimulation of TGF-2
(10 ng/mL). Boyden chamber and scratch assay were used to evaluate the migration
of RPE cells, while cell viability and apoptosis of RPE cells were measured by
MTT and TUNEL assay, respectively. Results: Treatment of RPE cells with
TM and TG (24 h) reduced the expression of -SMA and FN, and increased
the expression of Occludin in a dose dependent manner at protein level, which was
highly associated with the expression of GRP78. Treatment with TGF-2
significantly increased the expression of -SMA and FN, and decreased
the expression of Occludin both in protein and mRNA levels, which was
significantly inhibited by a 4h pre-treatment with TM. In addition, the
expression of TGF-RII and Smad2/3, and mRNAs of TGF-RII and
Smad3 were also decreased by the TM treatment. TM-induced ER stress inhibited RPE
cell migration, and high concentrations of TM and TG reduced cell viability and
induced apoptosis of RPE cells. Conclusions: Chemical induction of ER
stress inhibited EMT and migration in RPE cells, possibly by inactivation of
TGF- signaling, suggesting that regulation of ER stress in RPE cells may
be a new approach to prevent the development of intraocular fibrosis.