Article
Cell Biology
Mark S. Filla, Kristy K. Meyer, Jennifer A. Faralli, Donna M. Peters
Summary: Studies indicate that activation of αvβ3 integrin signaling may significantly impact TM cell function and POAG pathogenesis; overexpression of CA-αvβ3 integrin leads to significant differential gene expression involving multiple signaling pathways.
Article
Biochemistry & Molecular Biology
Philip Mzyk, Emma G. Zalog, Colleen M. McDowell
Summary: This study identified A20 as a molecular target that can attenuate the fibrotic response induced by TGF beta 2-TLR4 signaling. Overexpression of A20 rescued the fibrotic response in TM cells when treated with TGF beta 2, LPS, or cFN-EDA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Mengqi Qin, Cynthia Yu-Wai-Man
Summary: Glaucoma is a chronic neurodegenerative disease that affects 1% of the world's population, characterized by the loss of retinal ganglion cells and visual field defects. Elevated intraocular pressure (IOP) is a major risk factor and a therapeutic target for hypertensive glaucoma. Fibrosis, characterized by excessive deposition of extracellular matrix components and myofibroblasts, can impair trabecular meshwork (TM) function and contribute to the pathogenesis of glaucoma. This paper provides an overview of current anti-fibrotic therapeutics targeting the TM, including their mechanisms, efficacy, and research progress.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Stefania Vernazza, Sara Tirendi, Mario Passalacqua, Francesco Piacente, Sonia Scarfi, Francesco Oddone, Anna Maria Bassi
Summary: Primary Open-Angle Glaucoma (POAG) is a neurodegenerative disease that can lead to visual field constriction and blindness. The pathogenesis of POAG is complex, mainly explained through mechanical and vascular theories. While trabecular meshwork (TM) cells are less sensitive to pressure elevation, oxidative stress (OS) damage is exacerbated by an increase in pressure, suggesting the pivotal role of TM in the glaucoma cascade.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Myoung Sup Shim, April Nettesheim, Angela Dixon, Paloma B. Liton
Summary: This study identified primary cilia as the mechanosensor for cyclic mechanical stretch-induced autophagy in trabecular meshwork cells. The cross-regulation between AKT1 and noncanonical SMAD2/3 signaling was found to be critical in primary cilia-mediated activation of autophagy by mechanical stretch. Removal of primary cilia disrupted the homeostatic intraocular pressure compensatory response, highlighting the importance of primary cilia-mediated autophagy in regulating intraocular pressure homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Jennifer A. Faralli, Mark S. Filla, Donna M. Peters
Summary: Integrins play an important role in the Trabecular Meshwork/Schlemm's canal of the eye, regulating intraocular pressure and potentially contributing to glaucoma. Intercellular communication between integrins can influence cell response to ECM changes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Philip Mzyk, Humberto Hernandez, Thanh Le, Jose Ricardo Ramirez, Colleen M. M. McDowell
Summary: This review examines the role of Toll-like receptor 4 (TLR4) signaling in the trabecular meshwork and its interplay with endogenous activators (damage-associated molecular patterns (DAMPs)) and extracellular matrix (ECM), as well as its effect on intraocular pressure.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Ophthalmology
Kate E. Keller, Donna M. Peters
Summary: The trabecular meshwork regulates the outflow of aqueous humour and changes in the extracellular matrix can lead to increased outflow resistance and glaucoma development.
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2022)
Article
Pharmacology & Pharmacy
Li Li, Qian Liu, Lijuan Shi, Xibin Zhou, Wei Wu, Xue Wang, Lihua Wang, Zhihong Wu
Summary: This study investigated the anti-fibrotic effects of baicalin on human trabecular meshwork (HTM) cells and the underlying regulatory mechanisms. The findings suggest that baicalin can prevent TGF-beta 2-induced extracellular matrix deposition and alpha-SMA expression in HTM cells by inhibiting the MyD88/NF-kappa B pathway.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Timur A. Mavlyutov, Justin J. Myrah, Anil K. Chauhan, Yang Liu, Colleen M. McDowell
Summary: The study showed that B6.EDA(+/+) mice exhibit increased ECM accumulation in the TM, elevated IOP, enhanced proinflammatory changes in the ONH, loss of RGCs, and ONH damage. These data suggest that B6.EDA(+/+) mice recapitulate many aspects of glaucomatous damage.
CELL AND BIOSCIENCE
(2022)
Article
Multidisciplinary Sciences
Pinkal D. Patel, Yen-Lin Chen, Ramesh B. Kasetti, Prabhavathi Maddineni, William Mayhew, J. Cameron Millar, Dorette Z. Ellis, Swapnil K. Sonkusare, Gulab S. Zode
Summary: TRPV4 channels play a crucial role in regulating intraocular pressure and can be activated by increased fluid flow. Impaired TRPV4 channel activity in glaucomatous patients contributes to elevated intraocular pressure, highlighting the importance of TRPV4-eNOS signaling in IOP regulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Ophthalmology
Rajiv Rangan, Rafael Sad do Valle, Tara Tovar-Vidales
Summary: This study investigated the expression of procollagen C-proteinase enhancer 1 (PCOLCE1) in human trabecular meshwork (TM) and its potential alteration in glaucomatous conditions. The findings suggest that PCOLCE1 is expressed in TM tissues and cells and its expression may be downregulated by TGF82 treatment.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Cell Biology
Monika Lakk, David Krizaj
Summary: In this study, it was found that mechanical stretch promoted F-actin polymerization, increased the number and size of focal adhesions, and stimulated the activation of the Rho-associated protein kinase (ROCK) in human TM cells. The activation of both TRPV4 and ROCK were required for zyxin translocation and an increase in the number/size of focal adhesions in stretched cells. These results reveal the complex signaling pathways involved in the mechanical tuning of TM cells.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Review
Immunology
Lixiang Wang, Xin Wei
Summary: Exosomes are small membrane-bound particles released by all live cells and play important roles in normal physiological activities and pathologies. In glaucoma, exosome-based crosstalk has been found to play crucial roles in various processes of the disease, including oxidative stress response and neuroinflammation. However, the factors determining the specificity of exosome-based crosstalk in glaucoma remain largely unknown. This review summarizes the latest research focus on exosome-based crosstalk in glaucoma pathogenesis, current progress of exosome-based therapy, and provides perspectives on the research gap.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Shayshadri Mallick, Malini Sharma, Ajay Kumar, Yiqin Du
Summary: Glaucoma is characterized by elevated intraocular pressure which can lead to vision loss and eventual blindness, and stem cell transplantation shows promise in repairing trabecular meshwork dysfunction and providing a more direct and effective treatment approach.
