Increased proinflammatory cytokines including VEGF have been shown to be potent inducers of tight junction damage.27 Loss of XBP1 in intestinal epithelial cells results in spontaneous inflammation and pathologic changes of inflammatory bowel disease.50 In retinal cells, activation of XBP1 suppresses nuclear factor kappa-B (NF-κB) signaling and endothelial inflammation.19 These results suggest that enhanced VEGF expression may contribute to pathology of RPE tight junctions in XBP1-deficient RPE cells. Here, NFKB1 is linked to inflammatory bowel disease.