biostudies-literatureZenkel MThe Glaucoma Foundation New York (The Barry Friedberg and Charlotte Moss Family Foundation)Deutsche ForschungsgemeinschaftThe Glaucoma Foundation New York5977https://www.ebi.ac.uk/biostudies/studies/S-EPMC9180992biostudies-literatureUnknown23(11)Pseudoexfoliation (PEX) syndrome, a stress-induced fibrotic matrix process, is the most common recognizable cause of open-angle glaucoma worldwide. The recent identification of PEX-associated gene variants uncovered the vitamin A metabolic pathway as a factor influencing the risk of disease. In this study, we analyzed the role of the retinoic acid (RA) signaling pathway in the PEX-associated matrix metabolism and evaluated its targeting as a potential candidate for an anti-fibrotic intervention. We provided evidence that decreased expression levels of RA pathway components and diminished RA signaling activity occur in an antagonistic crosstalk with TGF-β1/Smad signaling in ocular tissues and cells from PEX patients when compared with age-matched controls. Genetic and pharmacologic modes ofInternational journal of molecular sciencesDysregulated Retinoic Acid Signaling in the Pathogenesis of Pseudoexfoliation Syndrome.PMC9180992SCHL 366/11-1; PA 2353/4-1N.A.SCHL 366/11-1PA 2353/4-1Weller JMSchlotzer-Schrehardt UPasutto FKonig LHohberger BGießl AHubner LOstermann TAKruse FEGusek-Schneider GCHoja UBerner DZenkel MfalseDysregulated Retinoic Acid Signaling in the Pathogenesis of Pseudoexfoliation Syndrome.Pseudoexfoliation (PEX) syndrome, a stress-induced fibrotic matrix process, is the most common recognizable cause of open-angle glaucoma worldwide. The recent identification of PEX-associated gene variants uncovered the vitamin A metabolic pathway as a factor influencing the risk of disease. In this study, we analyzed the role of the retinoic acid (RA) signaling pathway in the PEX-associated matrix metabolism and evaluated its targeting as a potential candidate for an anti-fibrotic intervention. We provided evidence that decreased expression levels of RA pathway components and diminished RA signaling activity occur in an antagonistic crosstalk with TGF-β1/Smad signaling in ocular tissues and cells from PEX patients when compared with age-matched controls. Genetic and pharmacologic modes of2022-01-01T00:00:00Z2022 May2025-04-25T19:02:00.544Z2025-02-19T04:56:41.845ZS-EPMC91809923568265710.3390/ijms23115977