Profile of cytokines in aqueous humor and trabecular meshwork cell culture in patients with pseudoexfoliation glaucoma

Glaucoma is one of the leading causes of irreversible blindness worldwide, being an age-related disease. Its pathogenesis still is not fully understood. A particular interest is attracted to evaluation of the cytokine concentrations in the trabecular meshwork cell culture, and in the aqueous humor (AH) taken from the same patient, since such data may allow to describe more completely the glaucomatous trabecular changes and to clarify the mechanisms of intercellular interactions in pseudoexfoliative (PEX) glaucoma. The purpose of this study was a comparative analysis of cytokine contents in AH and in trabecular tissue (TT) supernatants in the patients with PEX glaucoma. The study included 23 eyes of patients with PEX glaucoma. The material studied was AH and supernatant of TT cell culture. The cytokine concentration was measured using a flow cytofluorimeter FacsCantoII (BD, USA) using the CBA method. SPSS version 19 software (IBM, USA) was used for the statistical data processing. Concentrations of cytokines (TNFα, IFNγ, IL-1β, IL-6, IL-8, IL- 10, VEGF, GM-CSF) were determined in AH and in the TT supernatant for each of the patients with PEX glaucoma. Only IL-6 and VEGF concentrations in AH were higher than those in the TT supernatant in patients with PEX glaucoma. The IL-6 concentration positively correlated with the VEGF and IL-8 concentrations in the TT supernatant. Correlations between other cytokines in the TT supernatant and AH were also identified and analyzed. Multiple regression analysis revealed that the duration of glaucoma and the IFNγ and TNFα concentrations in AH may have a significant influence on the corneal endothelial cells, being associated with density reduction in patients with PEX glaucoma. The correlation analysis did not reveal any links between other clinical data (corneal thickness in the optical center, IOP level, age) and the cytokine concentrations in the studied tissues. The obtained results suggest that only simultaneous analysis of the cytokine concentrations in the TT supernatant and AH taken from the same patient may provide a more complete description of the cytokine imbalance and pathological processes occurring in the trabecular meshwork in PEX glaucoma patients. It has been shown that the changing cytokine ratios observed in PEX glaucoma may be associated with development of uniform structural and functional changes in all tissues of the anterior eye segment.

Download Full-text

IMMMUNE MEDIATORS IN IDIOPATHIC UVEITIS

10.1101/2021.08.04.455093 ◽

2021 ◽

Author(s):

Marie-Helene Errera ◽

Ana Pratas ◽

Sylvain Fisson ◽

Thomas Manicom ◽

Marouane Boubaya ◽

...

Keyword(s):

Aqueous Humor ◽

Unsupervised Classification ◽

Control Group ◽

Serum Samples ◽

Gm Csf ◽

Cytokines And Chemokines ◽

Age Related ◽

Order Of Magnitude ◽

Ifn Γ ◽

Endothelial Growth Factor

To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine proﬁles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all conﬁrmed by intraocular ﬂuid analyses. Noninfectious controls consisted of 7 patients with Behçet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninﬂammatory control patients with age-related cataract. In each sample, 27 immune mediators ± IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinﬂammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF-α and VEGF, were signiﬁcantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were signiﬁcantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinﬂammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-γ-inducing cytokine (IL12) and IFN-γ-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one speciﬁc uveitis entity.

Download Full-text

The Effect of Hyaluronic Acid on MMP-9 Expression in Trabecular Meshwork Cell Culture of Patient with Primary Open Angle Glaucoma

Journal of Agromedicine and Medical Sciences ◽

10.19184/ams.v3i1.4096 ◽

2017 ◽

Vol 3 (1) ◽

pp. 38

Author(s):

Cicih Komariah ◽

Ma’sum Effendi ◽

Hidayat Sujuti

Keyword(s):

Cell Culture ◽

Extracellular Matrix ◽

Hyaluronic Acid ◽

Trabecular Meshwork ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Open Angle ◽

Trabecular Meshwork Cell ◽

Matrix Deposition ◽

Extracellular Matrix Deposition

In primary open angle glaucoma, decrease of hyaluronic acid level is related to extracellular matrix deposition of trabecular meshwork. Extracellular matrix deposition will increase humor aqueous outflow resistance which in turn increase the intraocular pressure. MMP-9 as one of matrix metalloproteinase (MMP) family, has a high potency to degrade the extracellular matrix. The expression of MMP-9 can be activated by hyaluronic acid through its binding with CD44 as hyaluronic main receptor. The aim of this research is to determine the effect of hyaluronic acid on MMP-9 expression in trabecular meshwork cell culture of patient with primary open angle glaucoma by immunocytochemical method. Trabecular meshwork cell culture were exposed to hyaluronic acid at four different concentration (0mg/ml, 1 mg/mL, 3 mg/mL, 6 mg/mL). After 24 hours incubated, we find a significant difference of MMP-9 expression between control group and group with hyaluronic acid. There was significant correlation between hyaluronic acid and MMP-9 expression. Hyaluronic acid exposure will increase MMP-9 expression in trabecular meshwork cell culture. This finding suggest that hyaluronic acid can influence the resistance of humor aqueous outflow in trabecular meshwork by up-regulating MMP-9 expression, and therefore will increase extracellular matrix degradation.Key words : hyaluronic acid, primary open angle glaucoma, MMP-9

Download Full-text

Modulation of Aqueous Humor Outflow by Ionic Mechanisms Involved in Trabecular Meshwork Cell Volume Regulation

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.04-0060 ◽

2004 ◽

Vol 45 (10) ◽

pp. 3650 ◽

Cited By ~ 37

Author(s):

David Soto ◽

Nu´ria Comes ◽

Elisa Ferrer ◽

Miguel Morales ◽

Artur Escalada ◽

...

Keyword(s):

Cell Volume ◽

Aqueous Humor ◽

Trabecular Meshwork ◽

Volume Regulation ◽

Cell Volume Regulation ◽

Trabecular Meshwork Cell ◽

Aqueous Humor Outflow ◽

Ionic Mechanisms

Download Full-text

Trabecular Meshwork Cell Culture in Glaucoma Research:

Ophthalmology ◽

10.1016/s0161-6420(84)34241-5 ◽

1984 ◽

Vol 91 (6) ◽

pp. 580-595 ◽

Cited By ~ 88

Author(s):

Jon R. Polansky ◽

Irmgard S. Wood ◽

Maria T. Maglio ◽

Jorge A. Alvarado

Keyword(s):

Cell Culture ◽

Trabecular Meshwork ◽

Trabecular Meshwork Cell

Download Full-text

Morpho-functional changes of cardiac telocytes in isolated atrial amyloidosis in patients with atrial fibrillation

Scientific Reports ◽

10.1038/s41598-021-82554-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tatyana V. Sukhacheva ◽

Natalia V. Nizyaeva ◽

Maria V. Samsonova ◽

Andrey L. Cherniaev ◽

Artem A. Burov ◽

...

Keyword(s):

Atrial Fibrillation ◽

Mitral Valve Regurgitation ◽

Ultrastructural Level ◽

Cardiomyocyte Hypertrophy ◽

Myocardial Remodeling ◽

Valve Regurgitation ◽

Atrial Myocardium ◽

Functional Changes ◽

Age Related ◽

Transitional Forms

AbstractTelocytes are interstitial cells with long, thin processes by which they contact each other and form a network in the interstitium. Myocardial remodeling of adult patients with different forms of atrial fibrillation (AF) occurs with an increase in fibrosis, age-related isolated atrial amyloidosis (IAA), cardiomyocyte hypertrophy and myolysis. This study aimed to determine the ultrastructural and immunohistochemical features of cardiac telocytes in patients with AF and AF + IAA. IAA associated with accumulation of atrial natriuretic factor was detected in 4.3–25% biopsies of left (LAA) and 21.7–41.7% of right (RAA) atrial appendage myocardium. Telocytes were identified at ultrastructural level more often in AF + IAA, than in AF group and correlated with AF duration and mitral valve regurgitation. Telocytes had ultrastructural signs of synthetic, proliferative, and phagocytic activity. Telocytes corresponded to CD117+, vimentin+, CD34+, CD44+, CD68+, CD16+, S100-, CD105- immunophenotype. No significant differences in telocytes morphology and immunophenotype were found in patients with various forms of AF. CD68-positive cells were detected more often in AF + IAA than AF group. We assume that in aged AF + IAA patients remodeling of atrial myocardium provoked transformation of telocytes into “transitional forms” combining the morphological and immunohistochemical features with signs of fibroblast-, histiocyte- and endotheliocyte-like cells.

Download Full-text

Circumferential trabecular meshwork cell density in the human eye

Experimental Eye Research ◽

10.1016/j.exer.2021.108494 ◽

2021 ◽

Vol 205 ◽

pp. 108494

Author(s):

Markus H. Kuehn ◽

Janice A. Vranka ◽

David Wadkins ◽

Thomas Jackson ◽

Lin Cheng ◽

...

Keyword(s):

Cell Density ◽

Trabecular Meshwork ◽

Human Eye ◽

Trabecular Meshwork Cell

Download Full-text

Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Life ◽

10.3390/life11030242 ◽

2021 ◽

Vol 11 (3) ◽

pp. 242

Author(s):

Salvatore Nesci ◽

Fabiana Trombetti ◽

Alessandra Pagliarani ◽

Vittoria Ventrella ◽

Cristina Algieri ◽

...

Keyword(s):

Oxidative Phosphorylation ◽

Atp Synthase ◽

Mitochondrial Permeability Transition ◽

Ros Generation ◽

Protonmotive Force ◽

Mitochondrial Oxidative Phosphorylation ◽

F1fo Atp Synthase ◽

Functional Changes ◽

Age Related ◽

Mitochondrial Functions

Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases.

Download Full-text

The Impact of Oxidative Stress on Blood-Retinal Barrier Physiology in Age-Related Macular Degeneration

Cells ◽

10.3390/cells10010064 ◽

2021 ◽

Vol 10 (1) ◽

pp. 64

Author(s):

Annamaria Tisi ◽

Marco Feligioni ◽

Maurizio Passacantando ◽

Marco Ciancaglini ◽

Rita Maccarone

Keyword(s):

Oxidative Stress ◽

Macular Degeneration ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Age Related Macular Degeneration ◽

Blood Retinal Barrier ◽

Functional Changes ◽

Beneficial Effects ◽

Age Related ◽

The Impact

The blood retinal barrier (BRB) is a fundamental eye component, whose function is to select the flow of molecules from the blood to the retina and vice-versa, and its integrity allows the maintenance of a finely regulated microenvironment. The outer BRB, composed by the choriocapillaris, the Bruch’s membrane, and the retinal pigment epithelium, undergoes structural and functional changes in age-related macular degeneration (AMD), the leading cause of blindness worldwide. BRB alterations lead to retinal dysfunction and neurodegeneration. Several risk factors have been associated with AMD onset in the past decades and oxidative stress is widely recognized as a key factor, even if the exact AMD pathophysiology has not been exactly elucidated yet. The present review describes the BRB physiology, the BRB changes occurring in AMD, the role of oxidative stress in AMD with a focus on the outer BRB structures. Moreover, we propose the use of cerium oxide nanoparticles as a new powerful anti-oxidant agent to combat AMD, based on the relevant existing data which demonstrated their beneficial effects in protecting the outer BRB in animal models of AMD.

Download Full-text