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

Scientific Reports
Ramesh B KasettiGulab S Zode

Abstract

Increased 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...Continue Reading

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Citations

Oct 21, 2019·Journal of Materials Science. Materials in Medicine·Shirin NourS Mohammad Moazzeni
Jul 2, 2019·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Carla Johanna Plüss, Stefan Kustermann
Jul 1, 2020·Micromachines·Renhao LuEsak Lee
Aug 25, 2020·Investigative Ophthalmology & Visual Science·Felix YemanyiVijay Krishna Raghunathan
May 11, 2018·The Journal of Biological Chemistry·Ramesh B KasettiGulab S Zode
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Sep 7, 2019·Pediatric Blood & Cancer·Minako SugiyamaAtsushi Manabe
Nov 21, 2020·Investigative Ophthalmology & Visual Science·Felix Yemanyi, VijayKrishna Raghunathan
Nov 7, 2020·Nature Communications·Ramesh B KasettiGulab S Zode
Mar 12, 2021·The American Journal of Pathology·Chenna Kesavulu SugaliWeiming Mao
Oct 8, 2019·Experimental Eye Research·Stephnie Michelle KennedyAnshoo Choudhary
Apr 16, 2021·Proceedings of the National Academy of Sciences of the United States of America·Pinkal D PatelGulab S Zode
May 1, 2021·International Journal of Molecular Sciences·Wioletta Rozpędek-KamińskaIreneusz Majsterek
Jul 5, 2021·Journal of Pharmacological Sciences·Wataru MorozumiMasamitsu Shimazawa
Dec 17, 2021·Biochemical Society Transactions·Abir Chakraborty, Adrienne Lesley Edkins

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Methods Mentioned

BETA
protein folding
co-immunoprecipitation
immunoprecipitation
Assay

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