scholarly journals An Innovative In Vitro Open-Angle Glaucoma Model (IVOM) Shows Changes Induced by Increased Ocular Pressure and Oxidative Stress

2021 ◽  
Vol 22 (22) ◽  
pp. 12129
Author(s):  
Stefania Vernazza ◽  
Sara Tirendi ◽  
Mario Passalacqua ◽  
Francesco Piacente ◽  
Sonia Scarfì ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Model ◽  
Early Stage ◽  
Open Angle Glaucoma ◽  
Anterior Segment ◽  
Open Angle ◽  
Glaucoma Diagnosis ◽  
Neuroprotective Drugs ◽  
Ocular Pressure

Primary Open-Angle Glaucoma (POAG) is a neurodegenerative disease, and its clinical outcomes lead to visual field constriction and blindness. POAG’s etiology is very complex and its pathogenesis is mainly explained through both mechanical and vascular theories. The trabecular meshwork (TM), the most sensitive tissue of the eye anterior segment to oxidative stress (OS), is the main tissue involved in early-stage POAG, characterized by an increase in pressure. Preclinical assessments of neuroprotective drugs on animal models have not always shown correspondence with human clinical studies. In addition, intra-ocular pressure management after a glaucoma diagnosis does not always prevent blindness. Recently, we have been developing an innovative in vitro 3Dadvanced human trabecular cell model on a millifluidicplatform as a tool to improve glaucoma studies. Herein, we analyze the effects of prolonged increased pressure alone and, in association with OS, on such in vitro platform. Moreover, we verify whethersuch damaged TM triggers apoptosis on neuron-like cells. The preliminary results show that TM cells are less sensitive to pressure elevation than OS, and OS-damaging effects were worsened by the pressure increase. The stressed TM releases harmful signals,which increase apoptosis stimuli on neuron-like cells, suggesting its pivotal role in the glaucoma cascade.

scholarly journals Crosstalk between MicroRNA and Oxidative Stress in Primary Open-Angle Glaucoma

2021 ◽  
Vol 22 (5) ◽  
pp. 2421
Author(s):  
Saray Tabak ◽  
Sofia Schreiber-Avissar ◽  
Elie Beit-Yannai
Keyword(s):  
Oxidative Stress ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Additional Treatment ◽  
Type I ◽  
Open Angle ◽  
Outflow Resistance ◽  
Stress Injury

Reactive oxygen species (ROS) plays a key role in the pathogenesis of primary open-angle glaucoma (POAG), a chronic neurodegenerative disease that damages the trabecular meshwork (TM) cells, inducing apoptosis of the retinal ganglion cells (RGC), deteriorating the optic nerve head, and leading to blindness. Aqueous humor (AH) outflow resistance and intraocular pressure (IOP) elevation contribute to disease progression. Nevertheless, despite the existence of pharmacological and surgical treatments, there is room for the development of additional treatment approaches. The following review is aimed at investigating the role of different microRNAs (miRNAs) in the expression of genes and proteins involved in the regulation of inflammatory and degenerative processes, focusing on the delicate balance of synthesis and deposition of extracellular matrix (ECM) regulated by chronic oxidative stress in POAG related tissues. The neutralizing activity of a couple of miRNAs was described, suggesting effective downregulation of pro-inflammatory and pro-fibrotic signaling pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), transforming growth factor-beta 2 (TGF-β2), Wnt/β-Catenin, and PI3K/AKT. In addition, with regards to the elevated IOP in many POAG patients due to increased outflow resistance, Collagen type I degradation was stimulated by some miRNAs and prevented ECM deposition in TM cells. Mitochondrial dysfunction as a consequence of oxidative stress was suppressed following exposure to different miRNAs. In contrast, increased oxidative damage by inhibiting the mTOR signaling pathway was described as part of the action of selected miRNAs. Summarizing, specific miRNAs may be promising therapeutic targets for lowering or preventing oxidative stress injury in POAG patients.

scholarly journals Diagnostic capability of different morphological parameters for primary open‐angle glaucoma in the Chinese population

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ruoshi Li ◽  
Xia Wang ◽  
Yahui Wei ◽  
Yuan Fang ◽  
Tian Tian ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Chinese Population ◽  
Primary Open Angle Glaucoma ◽  
Early Stage ◽  
Open Angle Glaucoma ◽  
Structural Parameters ◽  
Open Angle ◽  
Fiber Layer ◽  
Diagnostic Capability ◽  
Diagnostic Power

Abstract Background To assess the diagnostic capability of novel Bruch’s membrane opening (BMO)-based disc parameters, the BMO-minimum rim width (BMO-MRW) and the BMO-minimum rim area (BMO-MRA) in the Chinese population and compare them to the retinal nerve fiber layer (RNFL) from optical coherence tomography (OCT) and the rim area (RA) from the Heidelberg retinal tomograph-III (HRT-III). Methods In total, 200 eyes of 77 healthy and 123 primary open-angle glaucoma (POAG) subjects were included in this cross-sectional study. All participants underwent the visual field test and structural measurements by OCT and HRT-III. The areas under the receiver operating characteristic curves (AUCs) of different structural parameters were calculated to assess their diagnostic power and compared using the DeLong test. Results In populations with different characteristics, the BMO-MRW and BMO-MRA had better diagnostic power than the RA. In discriminating between all POAG subjects and healthy controls and between early-stage patients and controls, the global BMO-MRW had comparable AUCs with the RNFL, but the BMO-MRA had lower AUCs than the RNFL. In healthy subjects with macrodiscs, both the global and sectoral BMO-MRW were thinner than those in healthy subjects with normal disc size. The AUCs of BMO-MRA, BMO-MRW and RNFL in subjects with macrodiscs were comparable. Additionally, in the myopic population, the BMO-MRA and BMO-MRW had comparable AUCs with the RNFL. Conclusions The BMO-MRW had comparable diagnostic power with the RNFL, and compared with BMO-MRW, the BMO-MRA might have advantages in certain populations, such as macrodiscs. All OCT-derived parameters exceeded the RA in diagnostic capability.

scholarly journals Effect of trabeculectomy and canaloplasty on intra-ocular pressure modifications after postural changes in open-angle glaucoma

2014 ◽  
Vol 92 (6) ◽  
pp. e498-e499 ◽  
Author(s):  
Luciano Quaranta ◽  
Elena Biagioli ◽  
Ivano Riva ◽  
Claudia Tosoni ◽  
Paolo Brusini ◽  
...  
Keyword(s):  
Open Angle Glaucoma ◽  
Open Angle ◽  
Intra Ocular Pressure ◽  
Postural Changes ◽  
Ocular Pressure

Antioxidant Status and Oxidative Stress in Primary Open Angle Glaucoma and Pseudoexfoliative Glaucoma

2011 ◽  
Vol 36 (8) ◽  
pp. 713-718 ◽  
Author(s):  
Mesut Erdurmuş ◽  
Ramazan Yağcı ◽  
Ömer Atış ◽  
Remzi Karadağ ◽  
Ali Akbaş ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Status ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Open Angle ◽  
Pseudoexfoliative Glaucoma ◽  
And Oxidative Stress

Primary Open-Angle Glaucoma and Sensitivity to Corticosteroids in Vitro

1977 ◽  
Vol 84 (5) ◽  
pp. 715-720 ◽  
Author(s):  
John G. Sowell ◽  
Ralph Z. Levene ◽  
Jeffrey Bloom ◽  
Michael Bernstein
Keyword(s):  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Open Angle

scholarly journals Antioxidative 1,4-Dihydropyridine Derivatives Modulate Oxidative Stress and Growth of Human Osteoblast-Like Cells In Vitro

Antioxidants ◽  
2018 ◽  
Vol 7 (9) ◽  
pp. 123 ◽  
Author(s):  
Lidija Milkovic ◽  
Tea Vukovic ◽  
Neven Zarkovic ◽  
Franz Tatzber ◽  
Egils Bisenieks ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Growth ◽  
Cell Model ◽  
Second Messengers ◽  
Human Osteoblast ◽  
Tert Butyl Hydroperoxide ◽  
Human Stress ◽  
Set Up ◽  
Dihydropyridine Derivatives

Oxidative stress has been implicated in pathophysiology of different human stress- and age-associated disorders, including osteoporosis for which antioxidants could be considered as therapeutic remedies as was suggested recently. The 1,4-dihydropyridine (DHP) derivatives are known for their pleiotropic activity, with some also acting as antioxidants. To find compounds with potential antioxidative activity, a group of 27 structurally diverse DHPs, as well as one pyridine compound, were studied. A group of 11 DHPs with 10-fold higher antioxidative potential than of uric acid, were further tested in cell model of human osteoblast-like cells. Short-term combined effects of DHPs and 50 µM H2O2 (1-h each), revealed better antioxidative potential of DHPs if administered before a stressor. Indirect 24-h effect of DHPs was evaluated in cells further exposed to mild oxidative stress conditions induced either by H2O2 or tert-butyl hydroperoxide (both 50 µM). Cell growth (viability and proliferation), generation of ROS and intracellular glutathione concentration were evaluated. The promotion of cell growth was highly dependent on the concentrations of DHPs used, type of stressor applied and treatment set-up. Thiocarbatone III-1, E2-134-1 III-4, Carbatone II-1, AV-153 IV-1, and Diethone I could be considered as therapeutic agents for osteoporosis although further research is needed to elucidate their bioactivity mechanisms, in particular in respect to signaling pathways involving 4-hydroxynoneal and related second messengers of free radicals.

scholarly journals Phytochemicals from the Cocoa Shell Modulate Mitochondrial Function, Lipid and Glucose Metabolism in Hepatocytes via Activation of FGF21/ERK, AKT, and mTOR Pathways

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 136
Author(s):  
Miguel Rebollo-Hernanz ◽  
Yolanda Aguilera ◽  
Maria A. Martin-Cabrejas ◽  
Elvira Gonzalez de Gonzalez de Mejia
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Cell Model ◽  
Fibroblast Growth Factor 21 ◽  
Alcoholic Fatty Liver ◽  
Atp Production ◽  
Cocoa Shell

The cocoa shell is a by-product that may be revalorized as a source of bioactive compounds to prevent chronic cardiometabolic diseases. This study aimed to investigate the phytochemicals from the cocoa shell as targeted compounds for activating fibroblast growth factor 21 (FGF21) signaling and regulating non-alcoholic fatty liver disease (NAFLD)-related biomarkers linked to oxidative stress, mitochondrial function, and metabolism in hepatocytes. HepG2 cells treated with palmitic acid (PA, 500 µmol L−1) were used in an NAFLD cell model. Phytochemicals from the cocoa shell (50 µmol L−1) and an aqueous extract (CAE, 100 µg mL−1) enhanced ERK1/2 phosphorylation (1.7- to 3.3-fold) and FGF21 release (1.4- to 3.4-fold) via PPARα activation. Oxidative stress markers were reduced though Nrf-2 regulation. Mitochondrial function (mitochondrial respiration and ATP production) was protected by the PGC-1α pathway modulation. Cocoa shell phytochemicals reduced lipid accumulation (53–115%) and fatty acid synthase activity (59–93%) and prompted CPT-1 activity. Glucose uptake and glucokinase activity were enhanced, whereas glucose production and phosphoenolpyruvate carboxykinase activity were diminished. The increase in the phosphorylation of the insulin receptor, AKT, AMPKα, mTOR, and ERK1/2 conduced to the regulation of hepatic mitochondrial function and energy metabolism. For the first time, the cocoa shell phytochemicals are proved to modulate FGF21 signaling. Results demonstrate the in vitro preventive effect of the phytochemicals from the cocoa shell on NAFLD.

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