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
Biochemistry & Molecular Biology
Judit Hodrea, Minh Ngoc Tran, Balazs Besztercei, Timea Medveczki, Attila J. Szabo, Laszlo Orfi, Illes Kovacs, Andrea Fekete
Summary: Primary open-angle glaucoma is a global issue without a definitive treatment. Increased intraocular pressure (IOP) is considered a primary risk factor, caused by fibrotic changes in the trabecular meshwork (TM). This study demonstrates that the sigma-1 receptor (S1R) agonist fluvoxamine (FLU) has anti-fibrotic effects in TM cells, reducing cell proliferation, migration, and fibrotic protein levels. The S1R protects against fibrosis by increasing nitric oxide production and facilitating extracellular matrix degradation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Pharmacology & Pharmacy
Longxiang Huang, Zhenni Wei, Xiaohui Wang, Chunlin Lan, Yihua Zhu, Qin Ye
Summary: This study demonstrates that AZD6738 can decrease intraocular pressure and inhibit fibrotic response in the eye, offering a potential therapeutic option for glaucoma treatment.
BIOCHEMICAL PHARMACOLOGY
(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
Mengxuan Liu, Megumi Honjo, Reiko Yamagishi, Nozomi Igarashi, Natsuko Nakamura, Makoto Kurano, Yutaka Yatomi, Koji Igarashi, Makoto Aihara
Summary: This study investigated the potential role of TGF-beta 3 in the fibrotic response of human trabecular meshwork cells and examined its relationship and interaction with ATX. The findings suggest that TGF-beta 3 can regulate the expression and signaling of ATX, leading to the upregulation of fibrogenic proteins. The study highlights the importance of trans-signaling between TGF-beta 3 and ATX in the development of trabecular meshwork fibrosis.
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
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
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
Xuejing Yan, Shen Wu, Qian Liu, Ying Cheng, Jingxue Zhang, Ningli Wang
Summary: The study demonstrates that the activation of autophagy is correlated with the pathogenesis of primary open angle glaucoma (POAG) associated with elevated intraocular pressure (IOP). The N450Y mutation of myocilin induces autophagy, which worsens cell viability. A transgenic mouse model with the N450Y myocilin mutation exhibits glaucoma phenotypes and altered aqueous humor dynamics.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
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
Cell Biology
Alyssa S. Aebersold, Zhao-Hui Song
Summary: This study found that non-psychotropic cannabidiol (CBD) has a positive effect on regulating intraocular pressure. It enhances aqueous humor outflow and modifies signaling pathways in trabecular meshwork (TM) cells.
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
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).
Review
Biochemistry & Molecular Biology
Nuria Comes, Antonio Serrano-Albarras, Jesusa Capera, Clara Serrano-Novillo, Enric Condom, Santiago Ramon y Cajal, Joan Caries Ferreres, Antonio Felipe
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2015)
Article
Cardiac & Cardiovascular Systems
Cristina Moreno, Anna Oliveras, Alicia de la Cruz, Chiara Bartolucci, Carmen Munoz, Eladia Salar, Juan R. Gimeno, Stefano Severi, Nuria Comes, Antonio Felipe, Teresa Gonzalez, Pier Lambiase, Carmen Valenzuela
CARDIOVASCULAR RESEARCH
(2015)
Article
Biochemistry & Molecular Biology
Ramon Martinez-Marmol, Nuria Comes, Katarzyna Styrczewska, Mireia Perez-Verdaguer, Ruben Vicente, Lluis Pujadas, Eduardo Soriano, Alexander Sorkin, Antonio Felipe
CELLULAR AND MOLECULAR LIFE SCIENCES
(2016)
Article
Hematology
Anna Oliveras, Meritxell Roura-Ferrer, Laura Sole, Alicia de la Cruz, Angela Prieto, Ainhoa Etxebarria, Joan Manils, Daniel Morales-Cano, Enric Condom, Concepcio Soler, Angel Cogolludo, Carmen Valenzuela, Alvaro Villarroel, Nuria Comes, Antonio Felipe
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2014)
Article
Cardiac & Cardiovascular Systems
Cristina Moreno, Alicia de la Cruz, Anna Oliveras, Sanjay R. Kharche, Miriam Guizy, Nuria Comes, Tomas Stary, Carlotta Ronchi, Marcella Rocchetti, Isabelle Baro, Gildas Loussouarn, Antonio Zaza, Stefano Severi, Antonio Felipe, Carmen Valenzuela
CARDIOVASCULAR RESEARCH
(2015)
Review
Biochemistry & Molecular Biology
A. Felipe, J. Bielanska, N. Comes, A. Vallejo, S. Roig, S. Ramon y Cajal, E. Condom, J. Hernandez-Losa, J. C. Ferreres
CURRENT MEDICINAL CHEMISTRY
(2012)
Article
Cell Biology
Nuria Comes, LaKisha K. Buie, Teresa Borras
Article
Cell Biology
Ramon Martinez-Marmol, Mireia Perez-Verdaguer, Sara R. Roig, Albert Vallejo-Gracia, Pelagia Gotsi, Antonio Serrano-Albarras, Maria Isabel Bahamonde, Antonio Ferrer-Montiel, Gregorio Fernandez-Ballester, Nuria Comes, Antonio Felipe
JOURNAL OF CELL SCIENCE
(2013)
Article
Cell Biology
Meritxell Roura-Ferrer, Laura Sole, Anna Oliveras, Rinat Dahan, Joanna Bielanska, Alvaro Villarroel, Nuria Comes, Antonio Felipe
JOURNAL OF CELLULAR PHYSIOLOGY
(2010)
Article
Physiology
Nuria Villalonga, Miren David, Joanna Bielanska, Ruben Vicente, Nuria Comes, Carmen Valenzuela, Antonio Felipe
JOURNAL OF GENERAL PHYSIOLOGY
(2010)
Article
Cell Biology
Albert Vallejo-Gracia, Joanna Bielanska, Javier Hernandez-Losa, Josep Castellvi, M. Carmen Ruiz-Marcellan, Santiago Ramon y Cajal, Enric Condom, Joan Manils, Concepcio Soler, Nuria Comes, Joan Carles Ferreres, Antonio Felipe
JOURNAL OF LEUKOCYTE BIOLOGY
(2013)
Article
Clinical Neurology
Meritxell Roura-Ferrer, Laura Sole, Anna Oliveras, Alvaro Villarroel, Nuria Comes, Antonio Felipe
Article
Multidisciplinary Sciences
Mireia Perez-Verdaguer, Jesusa Capera, Ramon Martinez-Marmol, Marta Camps, Nuria Comes, Michael M. Tamkun, Antonio Felipe
SCIENTIFIC REPORTS
(2016)
Article
Multidisciplinary Sciences
Ramon Martinez-Marmol, Katarzyna Styrczewska, Mireia Perez-Verdaguer, Albert Vallejo-Gracia, Nuria Comes, Alexander Sorkin, Antonio Felipe
SCIENTIFIC REPORTS
(2017)
Article
Physiology
Antonio Felipe, Concepcio Soler, Nuria Comes
FRONTIERS IN PHYSIOLOGY
(2010)