Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-Seq Transcriptomic Analysis of Human Trabecular Meshwork Explants Exposed to TGF-β2: A Novel Approach Beyond Traditional Cell Culture Models

ABSTRACT: Glaucoma is a progressive optic neuropathy that can lead to irreversible blindness. Its main risk factor is elevated intraocular pressure (IOP). The trabecular meshwork (TM) acts as a filter between the anterior chamber of the eye and the aqueous humor collecting ducts, and dysfunction of this meshwork is responsible for the increased IOP in primary open-angle glaucoma (POAG). Considering that the culture conditions of human TM cells (HTMC) influence gene expression, we used human TM explants (HTMEx), which most closely mimic physiological conditions, to study the transcriptome of HTMC. The transforming growth factor-beta 2 (TGF-β2) signaling pathway has been implicated in the pathophysiology of POAG. To better characterize the role of TGF-β2 in this pathophysiology, we used bulk RNA sequencing and immunohistological analyses to establish gene signatures of TGF-β2-exposed HTMEx and correlate them with morphological alterations. We identified differentially upregulated genes primarily involved in ECM regulation, as well as profibrotic TGF-β signaling pathways, confirmed using confocal microscopy to highlight changes in trabecular architecture, TGFβ2-induced F-actin rearrangements, and extracellular matrix (ECM) deposition. Enrichment analysis also revealed modulations of gene expression related to cytoskeletal organization, as well as activation of the bone morphogenic protein (BMP) and Wnt signaling pathways in response to TGF-β2.

ORGANISM(S): Homo sapiens

PROVIDER: GSE236302 | GEO | 2023/07/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Effects of dexamethasone for primary trabecular meshwork cell gene expression

Project description:To clarify the effects of dexamethasone treatment for primary trabecular meshwork cell gene expression, which may relates to the pathophysiology of glucocorticoid-induced glaucoma Three lots (lot #2584, 3423 and 4973) of primary culture human trabecular meshwork (TM) cells were purchased from ScienCell Research Laboratories (Carlsbad, CA). The TM cells were treated with and without 100nM dexamethasone (DEX) for 14 days. Genomewide gene expression analysis was carried out using Agilent 8X60K array.

2015-01-24 | E-GEOD-65240 | biostudies-arrayexpress

Transcription profiling of human trabecular meshwork cells after TGF-beta1 and 2 treatment

Project description:TGF-beta levels are known to increase in the aqueous humor of eye cells in patients with glaucoma. Increase TGF-beta is assumed to have a biochemical impact on the trabecular meshwork, and an increase in extracellular matrix formation, which may be responsible for decrease outflow facility of the eye. This may increase extracellular pressure, causing glaucoma. TGF-beta 1 may be the cause of abnormal accumulation of extracellular matrices in trabecular meshwork of eyes with primary open angle glaucoma. Transforming growth factor (TGF)-beta2 regulates the expression of proteoglycans in aqueous humor from human glaucomatous eyes. To identify gene expression changes as a result of TGF-beta1 and 2 treatment of human trabecular meshwork cells. We expect to see a change in expression of the proteoglycans in HTM cells as a response to TGF-beta treatment. Human Trabecular Meswork cells in the eye were bathed by aqueous humor. TM cells were removed from individuals with the following ages: 16,66,67,73, and 76. Each individual was treated with EtOH (control), TGF-beta1, or TGF-beta2. Total RNA from each individual was pooled for each chip. Technical replicates were created for each treatment type, for a total of 6 chips.

2008-06-15 | E-GEOD-7144 | biostudies-arrayexpress

Construction of miRNA-mRNA Regulatory Network Indicates Potential Biomarkers for Primary Open-Angle Glaucoma

Project description:MicroRNAs were associated with the development and progression of glaucoma. Our study aims to identify the potential miRNAs and target genes in human trabecular meshwork related to primary open-angle glaucoma (POAG).

2023-05-05 | GSE231760 | GEO

The potential role of long noncoding RNAs in primary open angle glaucoma

Project description:Long non-coding RNAs were associated with the development and progression of glaucoma. Our study aim to identify the potential genes in human trabecular meshwork related to primary open-angle glaucoma (POAG).

2019-09-28 | GSE138125 | GEO

Multi-omics analyses reveal the mechanical-stress-dependent changes in trabecular meshwork cytoskeletal-extracellular matrix interactions

Project description:Trabecular meshwork (TM) tissue is subjected to constant mechanical stress due to the ocular pulse created by the cardiac cycle. This induces alterations in membrane lipids and associated cell-cell adhesion and cell-extracellular matrix (ECM) interactions triggering intracellular signaling responses to counter mechanical insults. A loss of such response can lead to elevated intraocular pressure (IOP), a major risk factor for primary open-angle glaucoma. The purpose of this study was to understand the response of TM under mechanical stretch using a multi-omics approach. We performed an unbiased mRNA sequencing for changes in transcripts, mass spectrometry (MS)-based quantitative proteomics for protein changes, and multiple reaction monitoring (MRM) profiling based MS and HPLC-based MS to identify lipid changes. With the help of the multi-omics data analysis on human TM cells under mechanical stress, we provide evidence for the regulation of TM actin cytoskeleton and ECM interactions at the mRNA and protein levels, which can further modulate the TM lipids contents effectively regulating the mechanical properties of TM membrane. Overall, in this study, we propose the mechanistic interplay of macromolecules to bring about a concerted cellular response in TM cells to achieve mechanotransduction and IOP regulation

2022-08-30 | PXD031347 | Pride

Transcriptome-wide study of the response of human trabecular meshwork cells to the substrate stiffness increase

Project description:Elevated intraocular pressure, a major risk factor of glaucoma, is caused by the abnormal function of trabecular outflow pathways. Human trabecular meshwork (HTM) tissue plays an important role in the outflow pathways. However, the molecular mechanisms that how TM cells respond to the elevated IOP are largely unknown. We cultured primary HTM cells on polyacrylamide gels with tunable stiffness corresponding to Young's moduli ranging from 1.1 to 50 kPa. Then next‐generation RNA sequencing (RNA‐seq) was performed to obtain the transcriptomic profiles of HTM cells. Bioinformatics analysis revealed that genes related to glaucoma including DCN, SPARC, and CTGF, were significantly increased with elevated substrate stiffness, as well as the global alteration of HTM transcriptome. Extracellular matrix (ECM)‐related genes were selectively activated in response to the elevated substrate stiffness, consistent with the known molecular alteration in glaucoma. Human normal and glaucomatous TM tissues were also obtained to perform RNA‐seq experiments and supported the substrate stiffness‐altered transcriptome profiles from the in vitro cell model. The current study profiled the transcriptomic changes in human TM cells upon increasing substrate stiffness. Global change of ECM‐related genes indicates that the in vitro substrate stiffness could greatly affect the biological processes of HTM cells. The in vitro HTM cell model could efficiently capture the main pathogenetic process in glaucoma patients, and provide a powerful method to investigate the underlying molecular mechanisms.

2019-12-16 | GSE123100 | GEO

TGF-beta1 and 2 treatment of human trabecular meshwork cells (Russell-3U24NS043571-01S1-2)

2007-02-28 | GSE7144 | GEO

TIPARP is involved in the regulation of intraocular pressure

Project description:Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. The molecular mechanism of elevated IOP is unclear, which impedes glaucoma therapy. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible Poly-ADP-ribose Polymerase (TIPARP), a member of the PARP family, catalyses mono-ADP-ribosylation. Here we showed that TIPARP was widely expressed in the cornea, trabecular meshwork, iris, retina, optic nerve, sclera, and choroid of human eyes. The expression of TIPARP was significantly upregulated in the blood and trabecular meshwork of patients with primary open angle glaucoma compared with that of healthy controls. Transcriptome analysis revealed that the expression of genes related to extracellular matrix deposition and cell adhesion was decreased in TIPARP-upregulated human trabecular meshwork (HTM) cells. Moreover, western blot analysis showed that collagen types I and IV, fibronectin, and α-SMA were increased in TIPARP downregulated or TIPARP-inhibited HTM cells. In addition, cross-linked actin networks were produced, and vinculin was upregulated in these cells. Subconjunctival injection of the TIPARP inhibitor RBN-2397 increased the IOP in Sprague–Dawley rats. Therefore, we identified TIPARP as a regulator of IOP through modulation of extracellular matrix and cell cytoskeleton proteins in HTM cells. These results indicate that TIPARP is a potential therapeutic target for ocular hypertension and glaucoma.

2022-12-28 | GSE218153 | GEO

Genome-wide DNA methylation in cultured human Schelmm's Canal endothelial cells and trabecular meshwork cells with or without glaucoma

Project description:Genome-wide DNA methylation profiling in cultured human Schelmm's Canal endothelial cells (SC) and trabecular meshwork (TM) cells derived from post-mortem eyes with or without glaucoma. Our study aimed to identify glaucoma-associated genes that were affected by DNA methylation.

2020-01-03 | GSE129183 | GEO

Genome-wide Expression of Trabecular Meshwork in POAG

Project description:This study compared genome-wide expression profiles of individuals with and without Primary Open-Angle Glaucoma (POAG). One POAG case (case #6 with two replicates #10 and #11) carried a Q368X myocilin mutation. This study compared the genome-wide expression in human trabecular meshwork tissue between 13 controls and 15 POAG cases. Six controls and one POAG cases had the expression performed from both left and right eyes. One technical replicate was done between two cases. The average from the biological replicates for each inidividual was used for analysis.

2013-08-31 | E-GEOD-27276 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data