Figure 8. A schematic depiction of RPE cell dysfunction induced by IFN-γ, TNF-α, and IL-1β. The proinflammatory cytokines increased
the expression of proepithelial–mesenchymal transition (EMT) transcription factor genes SNAI1 and ZEB1 in the RPE cells. This could result in the downregulation of the epithelial marker gene CDH1 and upregulation of the mesenchymal marker genes VIM, CDH2, and CCND1. Increased ZEB1 expression also caused a decrease in the expression of the MITF gene that encodes a transcription factor that controls RPE differentiation. This, in turn, may decrease the expression of
the RPE functional genes RPE65, TYR, MERTK, RDH5, RDH10, TRPM1, and TRPM3. The decrease in MITF expression may also reduce the expression of miR-204 and miR-211, two microRNAs necessary for maintaining epithelial physiology
and RPE function.