Increased synthesis and deposition of extracellular matrix proteins leads to endoplasmic reticulum stress in the trabecular meshwork

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dc.creatorKasetti, Ramesh B.
dc.creatorMaddineni, Prabhavathi
dc.creatorMillar, J. Cameron
dc.creatorClark, Abbot F.
dc.creatorZode, Gulab S.
dc.creator.orcid0000-0003-3594-6560 (Clark, Abbot F.)
dc.creator.orcid0000-0002-7823-2595 (Zode, Gulab S.)
dc.date.accessioned2022-11-28T20:48:03Z
dc.date.available2022-11-28T20:48:03Z
dc.date.issued2017-11-02
dc.description.abstractIncreased synthesis and deposition of extracellular matrix (ECM) proteins in the trabecular meshwork (TM) is associated with TM dysfunction and intraocular pressure (IOP) elevation in glaucoma. However, it is not understood how ECM accumulation leads to TM dysfunction and IOP elevation. Using a mouse model of glucocorticoid (GC)-induced glaucoma, primary human TM cells and human post-mortem TM tissues, we show that increased ECM accumulation leads to endoplasmic reticulum (ER) stress in the TM. The potent GC, dexamethasone (Dex) increased the secretory protein load of ECM proteins in the ER of TM cells, inducing ER stress. Reduction of fibronectin, a major regulator of ECM structure, prevented ER stress in Dex-treated TM cells. Overexpression of fibronectin via treatment with cellular fibronectin also induced chronic ER stress in primary human TM cells. Primary human TM cells grown on ECM derived from Dex-treated TM cells induced ER stress markers. TM cells were more prone to ER stress from ECM accumulation compared to other ocular cell types. Moreover, increased co-localization of ECM proteins with ER stress markers was observed in human post-mortem glaucomatous TM tissues. These data indicate that ER stress is associated with increased ECM accumulation in mouse and human glaucomatous TM tissues.
dc.description.sponsorshipThese studies were supported by the National Eye Institute (EY022077 and EY026177) and funding from the North Texas Eye Research Institute in Fort Worth, TX.
dc.identifier.citationKasetti, R. B., Maddineni, P., Millar, J. C., Clark, A. F., & Zode, G. S. (2017). Increased synthesis and deposition of extracellular matrix proteins leads to endoplasmic reticulum stress in the trabecular meshwork. Scientific reports, 7(1), 14951. https://doi.org/10.1038/s41598-017-14938-0
dc.identifier.issn2045-2322
dc.identifier.issue1
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31987
dc.identifier.volume7
dc.publisherSpringer Nature
dc.relation.urihttps://doi.org/10.1038/s41598-017-14938-0
dc.rights.holder© The Author(s) 2017
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientific Reports
dc.subject.meshAnimals
dc.subject.meshCells, Cultured
dc.subject.meshDisease Models, Animal
dc.subject.meshEndoplasmic Reticulum Stress
dc.subject.meshExtracellular Matrix Proteins / analysis
dc.subject.meshExtracellular Matrix Proteins / metabolism
dc.subject.meshGlaucoma / metabolism
dc.subject.meshGlaucoma / pathology
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshProtein Biosynthesis
dc.subject.meshTrabecular Meshwork / metabolism
dc.subject.meshTrabecular Meshwork / pathology
dc.titleIncreased synthesis and deposition of extracellular matrix proteins leads to endoplasmic reticulum stress in the trabecular meshwork
dc.typeArticle
dc.type.materialtext

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