دورية أكاديمية
Expression of Mutant Myocilin Induces Abnormal Intracellular Accumulation of Selected Extracellular Matrix Proteins in the Trabecular Meshwork
| العنوان: | Expression of Mutant Myocilin Induces Abnormal Intracellular Accumulation of Selected Extracellular Matrix Proteins in the Trabecular Meshwork |
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| المؤلفون: | Kasetti, Ramesh B., Phan, Tien N., Millar, J. Cameron, Zode, Gulab S. |
| المصدر: | Investigative Ophthalmology & Visual Science |
| بيانات النشر: | Association for Research in Vision and Ophthalmology |
| سنة النشر: | 2022 |
| المجموعة: | UNTHSC Scholarly Repository (University. of North Texas Health Science Center) |
| مصطلحات موضوعية: | myocilin, ECM, glaucoma, trabecular meshwork, ER stress, Animals, Aqueous Humor / metabolism, Blotting, Western, Cells, Cultured, Cytoskeletal Proteins / biosynthesis, Cytoskeletal Proteins / genetics, DNA / genetics, DNA Mutational Analysis, Disease Models, Animal, Endoplasmic Reticulum Chaperone BiP, Endoplasmic Reticulum Stress, Extracellular Matrix Proteins / genetics, Extracellular Matrix Proteins / metabolism, Eye Proteins/biosynthesis / genetics, Gene Expression Regulation, Open-Angle / genetics, Open-Angle / metabolism, Open-Angle / physiopathology, Glycoproteins / biosynthesis, Glycoproteins / genetics, Humans, Intraocular Pressure |
| الوصف: | PURPOSE: Abnormal accumulation of extracellular matrix (ECM) in the trabecular meshwork (TM) is associated with decreased aqueous humor outflow facility and IOP elevation in POAG. Previously, we have developed a transgenic mouse model of POAG (Tg-MYOCY437H) by expressing human mutant myocilin (MYOC), a known genetic cause of POAG. The purpose of this study is to examine whether expression of mutant myocilin leads to reduced outflow facility and abnormal ECM accumulation in Tg-MYOCY437H mice and in cultured human TM cells. METHODS: Conscious IOP was measured at various ages of Tg-MYOCY437H mice using a rebound tonometer. Outflow facility was measured in 10-month-old Tg-MYOCY437H mice. Selected ECM proteins were examined in human TM-3 cells stably expressing mutant myocilin and primary human TM cells (n = 4) as well as in the TM of Tg-MYOCY437H mice by real-time PCR, Western blotting, and immunostaining. Furthermore, TM cells expressing WT or mutant myocilin were treated with 5 mM sodium 4-phenylbutyrate (PBA), and ECM proteins were examined by Western blot and immunostaining. RESULTS: Starting from 3 months of age, Tg-MYOCY437H mice exhibited significant IOP elevation compared with wild-type (WT) littermates. Outflow facility was significantly reduced in Tg-MYOCY437H mice (0.0195 mul/min/mm Hg in Tg-MYOCY437H vs. 0.0332 mul/min/mm Hg in WT littermates). Increased accumulation of fibronectin, elastin, and collagen type IV and I was observed in the TM of Tg-MYOCY437H mice compared with WT littermates. Furthermore, increased ECM proteins were also associated with induction of endoplasmic reticulum (ER) stress markers, GRP78 and CHOP in the TM of Tg-MYOCY437H mice. Human TM-3 cells stably expressing DsRed-tagged Y437H mutant MYOC exhibited inhibition of myocilin secretion and its intracellular accumulation compared with TM cells expressing WT MYOC. Expression of mutant MYOC in TM-3 cells or human primary TM cells induced ER stress and also increased intracellular protein levels of fibronectin, elastin, laminin, and ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| تدمد: | 1552-5783 |
| العلاقة: | https://doi.org/10.1167/iovs.16-19610Test; Kasetti, R. B., Phan, T. N., Millar, J. C., & Zode, G. S. (2016). Expression of Mutant Myocilin Induces Abnormal Intracellular Accumulation of Selected Extracellular Matrix Proteins in the Trabecular Meshwork. Investigative ophthalmology & visual science, 57(14), 6058-6069. https://doi.org/10.1167/iovs.16-19610Test; https://hdl.handle.net/20.500.12503/31988Test; 57; 14 |
| الإتاحة: | https://doi.org/20.500.12503/31988Test https://doi.org/10.1167/iovs.16-19610Test https://hdl.handle.net/20.500.12503/31988Test |
| حقوق: | Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; © The Author(s). 2016. |
| رقم الانضمام: | edsbas.F2829C83 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15525783 |
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