Article
Pharmacology & Pharmacy
Qin-Xuan Xia, Jing Yu, Zhao-Jun Wang, Qi-Wen Guan, Xiao-Yuan Mao
Summary: This study demonstrates that LOXs have significant predictive value for prognosis, chemotherapy, and immunotherapy in glioma patients.
FRONTIERS IN PHARMACOLOGY
(2022)
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
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)
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)
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)
Article
Multidisciplinary Sciences
Tave van Zyl, Wenjun Yan, Alexi M. McAdams, Aboozar Monavarfeshani, Gregory S. Hageman, Joshua R. Sanes
Summary: In this study, we generated an anterior segment cell atlas of the human eye using high-throughput single-nucleus RNA sequencing (snRNAseq) and identified over 60 cell types. The atlas revealed the cell type characteristics of different tissues in the anterior segment and the sharing of certain cell types across tissues. Additionally, the atlas was used to investigate cell type-specific expression patterns of genes associated with ocular diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
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.
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)
Article
Biochemistry & Molecular Biology
Mi Sun Sung, So Young Kim, Gwang Hyeon Eom, Sang Woo Park
Summary: This study aimed to investigate the effects of different concentrations of vascular endothelial growth factor (VEGF) on human trabecular meshwork (TM) cells and explored the role of the Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway in VEGF-induced fibrosis. The results showed that high VEGF concentrations increased TAZ expression and decreased p-TAZ/TAZ expression, while fibrotic and ECM protein expression increased. CLAN formation also increased. Furthermore, inhibiting TAZ with verteporfin rescued TM cells from high-VEGF-concentration-induced fibrosis. These findings suggest that VEGF has dose-dependent effects on TM cells and TAZ inhibition may be a potential therapeutic target for VEGF-induced TM dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Cell Biology
Maria F. Suarez, Heather M. Schmitt, Megan S. Kuhn, Teddijo Watkins, Kristyn M. Hake, Tara Weisz, Edward J. Flynn III, Michael H. Elliott, Michael A. Hauser, W. Daniel Stamer
Summary: Pseudoexfoliation syndrome is an age-related disorder characterized by elastosis and extracellular matrix deposits. Variants in the LOXL1 gene play a significant role in the development of aggressive glaucoma associated with this syndrome. The abundance of LOXL1 and genetic context are important factors affecting the repair of elastin-containing tissues.
DISEASE MODELS & MECHANISMS
(2023)
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
Biochemistry & Molecular Biology
Prity Sahay, Munmun Chakraborty, Aparna Rao
Summary: Pseudoexfoliation (PXF) is a condition characterized by the accumulation of exfoliative material in the eye, which can lead to high rates of blindness if untreated. Pseudoexfoliation glaucoma (PXG) is often diagnosed late, highlighting the need for new screening tools for early detection. This study used a proteomics strategy to identify proteins involved in PXF and PXG pathogenesis, providing insights for early detection and prevention of glaucoma.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Pharmacology & Pharmacy
Jinyuan Luo, Greymi Tan, Kai Xin Thong, Konstantinos N. Kafetzis, Neeru Vallabh, Carl M. Sheridan, Yusuke Sato, Hideyoshi Harashima, Aristides D. Tagalakis, Cynthia Yu-Wai-Man
Summary: This study demonstrates the successful delivery of MRTF-B siRNA into human trabecular meshwork cells using a novel lipid nanoparticle (LNP). The results show that both LNP formulations effectively silenced the MRTF-B gene without cytotoxicity. The study also found that LNP significantly reduced cell contractility. These findings suggest that LNP could be a promising non-viral gene therapy for preventing fibrosis in minimally invasive glaucoma surgery (MIGS).
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)
