Attribution 4.0 International (CC BY 4.0)2022-09-202022-09-202022-07-07McKay, T. B., Kivanany, P. B., Nicholas, S. E., Nag, O. K., Elliott, M. H., Petroll, W. M., & Karamichos, D. (2022). Quercetin Decreases Corneal Haze In Vivo and Influences Gene Expression of TGF-Beta Mediators In Vitro. Metabolites, 12(7), 626. https://doi.org/10.3390/metabo120706262218-1989https://hdl.handle.net/20.500.12503/31793We have previously reported the flavonoid, quercetin, as a metabolic regulator and inhibitor of myofibroblast differentiation in vitro. Our current study evaluated the effects of topical application of quercetin on corneal scar development using two different animal models followed by RNA analysis in vitro. Wild-type C57BL/6J mice were anesthetized and the corneal epithelium and stroma were manually debrided, followed by quercetin (0.5, 1, 5, or 50 mM) or vehicle application. Corneal scarring was assessed for 3 weeks by slit lamp imaging and clinically scored. In a separate animal study, six New Zealand White rabbits underwent lamellar keratectomy surgery, followed by treatment with 5 mM quercetin or vehicle twice daily for three days. Stromal backscattering was assessed at week 3 by in vivo confocal microscopy. In mice, a single dose of 5 mM quercetin reduced corneal scar formation. In rabbits, stromal backscattering was substantially lower in two out of three animals in the quercetin-treated group. In vitro studies of human corneal fibroblasts showed that quercetin modulated select factors of the transforming growth factor-beta (TGF-beta) signaling pathway. These results provide evidence that quercetin may inhibit corneal scarring. Further studies in a larger cohort are required to validate the efficacy and safety of quercetin for clinical applications.http://creativecommons.org/licenses/by/4.0/antifibroticcorneal debridementcorneal wound healingflavonoidkeratectomyquercetintransforming growth factor-betaArticle© 2022 by the authors.127