02116nas a2200229   4500000000100000000000100001008004100002260001500043653002700058653001600085653001800101100002500119700002200144700001800166700002100184245008400205856005500289300000900344490000700353520151200360022001401872       2024                            d  c2024-02-2010aBiomedical Engineering10adrug safety10aLab-on-a-chip1 aRodi Kado Abdalkader1 aRomanas Chaleckis1 aTakuya Fujita1 aKen-ichiro Kamei00aModeling dry eye with an air–liquid interface in corneal epithelium-on-a-chip  uhttps://www.nature.com/articles/s41598-024-54736-z  a41850 v143 aDry eye syndrome (DES) is a complex ocular condition characterized by an unstable tear film and inadequate tear production, leading to tissue damage. Despite its common occurrence, there is currently no comprehensive in vitro model that accurately reproduce the cellular characteristics of DES. Here we modified a corneal epithelium-on-a-chip (CEpOC) model to recapitulate DES by subjecting HCE-T human corneal epithelial cells to an air–liquid (AL) interface stimulus. We then assessed the effects of AL stimulation both in the presence and absence of diclofenac (DCF), non-steroidal anti-inflammatory drug. Transcriptomic analysis revealed distinct gene expression changes in response to AL and AL_DCF, affecting pathways related to development, epithelial structure, inflammation, and extracellular matrix remodeling. Both treatments upregulated PIEZO2, linked to corneal damage signaling, while downregulating OCLN, involved in cell–cell junctions. They increased the expression of inflammatory genes (e.g., IL-6) and reduced mucin production genes (e.g., MUC16), reflecting dry eye characteristics. Metabolomic analysis showed increased secretion of metabolites associated with cell damage and inflammation (e.g., methyl-2-oxovaleric acid, 3-methyl-2-oxobutanoic acid, lauroyl-carnitine) in response to AL and even more with AL_DCF, indicating a shift in cellular metabolism. This study showcases the potential use of AL stimulus within the CEpOC to induce cellular characteristics relevant to DES.  a2045-2322