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
Ophthalmology
Myoung Sup Shim, Paloma B. Liton
Summary: The autophagy lysosomal system plays a crucial role in maintaining eye pressure and glaucoma development. This review discusses the mechanisms by which autophagy regulates normal tissue function in aqueous humor outflow pathway and its response to stressors. Additionally, it explores the roles of autophagy and lysosomal enzymes in cellular signaling and extracellular matrix remodeling, as well as the link between autophagy dysfunction and cellular senescence. Pre-clinical animal models are used to investigate how dysregulated autophagy contributes to disease, and its application in human glaucoma is discussed. Finally, the challenges and potential of autophagy as a therapeutic target for ocular hypertension and glaucoma are considered.
PROGRESS IN RETINAL AND EYE RESEARCH
(2022)
Article
Cell Biology
Ruotian Du, Dongyan Li, Meng Zhu, Lisha Zheng, Keli Ren, Dong Han, Long Li, Jing Ji, Yubo Fan
Summary: The mechanical microenvironment and cellular senescence play a vital role in the development of primary open-angle glaucoma. This study found that shear stress has a more significant effect on normal cells compared to senescent cells. Additionally, senescent cells show reduced extracellular matrix turnover after shear stress stimulation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rachel Curnock, Katy Yalci, Johan Palmfeldt, Marja Jaattela, Bin Liu, Bernadette Carroll
Summary: The accumulation of senescent cells is a driver of aging, and one characteristic of senescent cells is an increase in lysosomal content. However, little is known about the causes and consequences of lysosomal biogenesis in senescence.
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)
Article
Biochemistry & Molecular Biology
Jose A. Martina, Eutteum Jeong, Rosa Puertollano
Summary: TFEB-S401 phosphorylation is linked to the transcriptional control of monocyte differentiation.
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
Biochemistry & Molecular Biology
Diego Sbardella, Grazia Raffaella Tundo, Massimo Coletta, Gianluca Manni, Francesco Oddone
Summary: Steroid-induced glaucoma is a severe eye condition characterized by rapidly increasing intraocular pressure due to metabolic dysregulation of Trabecular Meshwork Cells. Exposure to steroids inhibits the autophagy process in TMCs, possibly through the Ubiquitin Proteasome System.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Eutteum Jeong, Jose A. Martina, Pablo S. Contreras, Juhyung Lee, Rosa Puertollano
Summary: TFEB and TFE3 interact with the FACT complex, regulating the transcription of stress-induced genes. FACT plays a crucial role in regulating cellular homeostasis.
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)
Review
Cell Biology
Suresh Kumar, Miguel Sanchez-alvarez, Fidel-Nicolas Lolo, Flavia Trionfetti, Raffaele Strippoli, Marco Cordani
Summary: Autophagy and the lysosomal system, known together as the autophagolysosomal system, play a crucial role in maintaining cellular health and homeostasis by clearing cellular waste. TFEB regulates this system by driving the expression of multiple genes, including components of the autophagolysosomal system. Reactive Oxygen Species (ROS) are key in the physiological and pathological roles of this system.
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)
Article
Biochemistry & Molecular Biology
Kristine Porter, Joshua Hirt, W. Daniel Stamer, Paloma B. Liton
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2015)
Article
Ophthalmology
Paloma B. Liton
EXPERIMENTAL EYE RESEARCH
(2016)
Article
Ophthalmology
Andrew M. Williams, Kristin M. Perkumas, Isaac Perry, Joanne C. Wen, Janet Keeling, Michael Tramber, Paloma B. Liton, W. Daniel Stamer
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
(2016)
Article
Ophthalmology
Joshua Hirt, Paloma B. Liton
EXPERIMENTAL EYE RESEARCH
(2017)
Article
Virology
Miguel Angel Munoz-Alia, Jose M. Casasnovas, Maria Luisa Celma, Juan Carabana, Paloma B. Liton, Rafael Fernandez-Munoz
Article
Biochemistry & Molecular Biology
Kristine M. Porter, Nallathambi Jeyabalan, Paloma B. Liton
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2014)
Article
Ophthalmology
Ping Xu, Yizhi Lin, Kristine Porter, Paloma B. Liton
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
(2014)
Article
Multidisciplinary Sciences
Kristine Porter, Yizhi Lin, Paloma B. Liton
Article
Cell Biology
Myoung Sup Shim, April Nettesheim, Joshua Hirt, Paloma B. Liton
Article
Multidisciplinary Sciences
April Nettesheim, Myoung Sup Shim, Josh Hirt, Paloma B. Liton
SCIENTIFIC REPORTS
(2019)
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
Kai Kaarniranta, Janusz Blasiak, Paloma Liton, Michael Boulton, Daniel J. Klionsky, Debasish Sinha
Summary: Age-related macular degeneration (AMD) is a leading cause of visual impairment in the aging population. The progression of AMD is characterized by atrophic alterations in the retinal pigment epithelium and the formation of lipofuscin and deposits. Chronic oxidative stress, protein aggregation, and inflammation may contribute to the development of AMD.
Review
Ophthalmology
Myoung Sup Shim, Paloma B. Liton
Summary: The autophagy lysosomal system plays a crucial role in maintaining eye pressure and glaucoma development. This review discusses the mechanisms by which autophagy regulates normal tissue function in aqueous humor outflow pathway and its response to stressors. Additionally, it explores the roles of autophagy and lysosomal enzymes in cellular signaling and extracellular matrix remodeling, as well as the link between autophagy dysfunction and cellular senescence. Pre-clinical animal models are used to investigate how dysregulated autophagy contributes to disease, and its application in human glaucoma is discussed. Finally, the challenges and potential of autophagy as a therapeutic target for ocular hypertension and glaucoma are considered.
PROGRESS IN RETINAL AND EYE RESEARCH
(2022)
Article
Cell Biology
Joshua Hirt, Kris Porter, Angela Dixon, Stuart McKinnon, Paloma B. Liton
CELL DEATH DISCOVERY
(2018)