Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA175384 | ENA |
REPOSITORIES: ENA
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Project description:Surgical glaucoma therapy is characterized by implantation of an aqueous shunt either draining into the extraocular Tenon’s space or the intraocular suprachoroidal space. In both cases the long term drainage is hampered by fibrotic reactions around the outflow region of the shunt. The prevention of fibrosis should extend the operating life of the shunt. For an aqueous shunt draining from the anterior chamber into the choroidal space fibroblasts from the choroidea and/or the sclera are most likely responsible for a fibrotic response around the outflow region of such a shunt. A detailed characterization of fibroblasts derived from choroidea and sclera should provide information whether a fibrosis reaction can be inhibited by cell type specific agents. Therefore, we have decided to generate mRNA profiles of fibroblasts from the choroidea, sclera and Tenon’s space in order to look for potential pharmacological targets for fibrosis prevention. The three fibroblast types investigated share fibroblast specific gene expression patterns, concerning extracellular matrix proteins as collagens and fibronectin, but also show distinct mRNA patterns, which we plan to search for targets responsible for fibrotic processes which hopefully can be targeted by specific antifibrotic drugs.
2012-09-25 | GSE40929 | GEO
Project description:Surgical glaucoma therapy is characterized by implantation of an aqueous shunt either draining into the extraocular Tenon’s space or the intraocular suprachoroidal space. In both cases the long term drainage is hampered by fibrotic reactions around the outflow region of the shunt. The prevention of fibrosis should extend the operating life of the shunt. For an aqueous shunt draining from the anterior chamber into the choroidal space fibroblasts from the choroidea and/or the sclera are most likely responsible for a fibrotic response around the outflow region of such a shunt. A detailed characterization of fibroblasts derived from choroidea and sclera should provide information whether a fibrosis reaction can be inhibited by cell type specific agents. Therefore, we have decided to generate mRNA profiles of fibroblasts from the choroidea, sclera and Tenon’s space in order to look for potential pharmacological targets for fibrosis prevention. The three fibroblast types investigated share fibroblast specific gene expression patterns, concerning extracellular matrix proteins as collagens and fibronectin, but also show distinct mRNA patterns, which we plan to search for targets responsible for fibrotic processes which hopefully can be targeted by specific antifibrotic drugs. Three human fibroblast cell type cultures from different ocular tissues were established: sclera fibroblasts (hSF), choroidea fibroblasts (hCF), and Tenon’s space fibroblasts (hTF). For the gene expression analysis n = 5 for hCF, n = 4 for hSF, and n = 5 for hTF donor cells were cultivated from different donors. After appropriate cultivation, cells were harvested, RNA was extracted, purified and quantity and quality was assessed. All total RNA samples were analyzed by Affymetrix' Whole-Transcript Expression Analysis & Profiling Human Gene ST Arrays, respectively. In this set-up, we run = 5 arrays for hCF, n = 4 arrays for hSF, and n = 5 arrays for hTF i.e. one array per biological replicate. No technical replication was carried out. Microarray data analysis was carried out by using the Rosetta Resolver® system for gene expression data analysis (Rosetta Biosoftware, Seattle, WA, USA). In brief, the raw signals of the probes were summarized using RMA thereby generating probe set specific signal intensities. Chips were normalized by using quantile normalization. To compare RNA expression levels of genes in hCF, hSF and hTF, normalized expression signals of genes from corresponding samples were averaged and fold changes were calculated. To assess differences in mean signal intensities between experimental groups, ANOVA (analysis of variance, with Benjamini Hochberg test correction) and a post-hoc Scheffe test was performed. Rosetta Resolver ratio built statistics to correct for possible signal intensity bias were also considered. Only genes (1) an absolute fold change of ≥ 1.5 together with a Scheffe test p value ≤ 0.05 in at least one of the three pairwise comparisons hCF vs. hTF, hSF vs. hTF and hCF vs. hSF, resp., as well as (2) a ratio built p value ≤ 0.05 were deemed differentially expressed genes (DEG) and considered for further evaluation.
2012-09-25 | E-GEOD-40929 | biostudies-arrayexpress
Project description:Trabecular meshwork cells in eyes with glaucoma aquire mesenchymal phenotypes. The types of microRNAs in exosomes may differ between static and glaucomatous status and their effects on aqueous humor regulation are still uknown. We used microarrays to identify the differential microRNA expression related to interaction between trabecular meshwork cells and Schlemm's canal endothelial cells.
2021-11-17 | GSE175464 | GEO
Project description:This study aimed to investigate changes in immune related genes on the ocular surface of patients with different diagnoses. We compared DEGs from 21 healthy controls, 12 aqueous tear deficient (ATD), and 12 Sjögren disease dry eye using the nanostring immunology v2 panel. We identified DEGs in immune pathways relating to viral response and adaptive immunity. We did not identify DEGs in comparison of ATD vs SjD, suggesting there are no differences in the immune response on the ocular surface, despite different diagnoses.
2025-12-01 | GSE311496 | GEO
Project description:Aqueous humor (AH) is the fluid in the anterior and posterior chambers of the eye that contains proteins regulating ocular homeostasis. Analysis of aqueous humor proteome is challenging mainly due to low sample volume and protein concentration. In this study, by utilizing state of the art technology, we performed Liquid-Chromatography Mass spectrometry (LC-MS/MS) analysis of 88 aqueous humor samples from subjects undergoing cataract surgery.
2021-09-09 | PXD022463 | Pride
Project description:Cardiac fibrosis is a major contributor to heart failure (HF), yet its therapeutic targeting remains limited due to the complexity of fibrosis types and distributions. This study investigates fibroblast heterogeneity and spatial organization in the left ventricle of human hearts from non-failing donors and HF patients with ischemic or dilated cardiomyopathy. Using single-nucleus RNA sequencing and spatial transcriptomics, distinct fibroblast subpopulations were identified, with resident fibroblasts being depleted in HF and replaced by disease-associated states. Differences in activation ligands, transcriptional trajectories, and spatial localization revealed divergent fibroblast transitions between scar and interstitial fibrosis, and between HF subtypes. These results provide insight into fibroblast dynamics and offer potential targets to modulate fibrosis in heart failure.
2025-11-08 | GSE298023 | GEO
Project description:PURPOSE: To investigate the circulatory microRNA (miRNA) profiles of aqueous, vitreous, and plasma in order to identify biomarkers in aqueous humor or plasma that are reflecting changes in vitreous of patients with diabetes. METHODS: Aqueous, vitreous and plasma samples were collected from a total of 27 patients - 11 controls (macular pucker or macular hole patients) and 16 patients with diabetes mellitus (DM) undergoing vitreoretinal surgery: DM-Type I with proliferative diabetic retinopathy (PDR) (DMI-PDR), DM Type II with PDR (DMII-PDR) and DM Type II with nonproliferative DR (DMII-NPDR). MiRNAs were isolated using Qiagen microRNeasy kit, quantified on BioAnalyzer, labeled with FlashTag kit, and profiled on Affymetrix GeneChip miRNA 3.0 microarrays. Data analysis was done using Expression Console (EC), Transcriptome Analysis Console (TAC), and Ingenuity Pathway Analysis (IPA) software. RESULTS: Our comparison of circulatory miRNA population of aqueous and vitreous humor and plasma showed that out of total of 847 human miRNA probes on the Affymetrix GeneChip miRNA 3.0 we found common miRNAs for both aqueous and vitreous samples, as well as larger number of unique miRNA, dependent on the DM type and presence of retinopathy. Most of the dysregulated miRNAs in aqueous and vitreous of DM patients were upregulated, while in plasma, most of the DM-specific miRNAs were downregulated. Dysregulation of miRNAs in aqueous generally do not appear to be a good representative of the miRNA abundance in vitreous, or plasma, although we did identify a few candidates for common biomarkers: let-7b, miR-320b, miR-762 and miR-4488. Additionally, each of the DR subtypes showed a set of miRNA that is uniquely dysregulated in each fluid, for example in aqueous samples for DMII-NPDR it was miR-455-3p, for DMII-PDR was miR-296, and for DMI-PDR it was miR-3202. Pathway analysis identified TGF-beta and VEGF pathways as the common targets for miRNAs dysregulated in DR aqueous and vitreous. CONCLUSIONS: The comparative profiling of circulatory miRNAs in aqueous, vitreous, and plasma showed that a small number of circulatory miRNAs displayed differential presence in controls vs. diabetic retinopathy. A pattern is emerging of sets of miRNA that are common or uniquely dysregulated in the blood plasma or ocular fluids of DR subtypes, offering promise for the use of ocular fluids and plasma for identifying diagnostic and therapeutic targets.
2020-06-27 | GSE140959 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by repetitive alveolar injuries with excessive deposition of extracellular matrix (ECM) proteins. A crucial need in understanding IPF pathogenesis is identifying cell types associated with histopathological regions, particularly local fibrosis centers known as fibroblast foci. To address this, we integrated published spatial transcriptomics and single-cell RNA sequencing (scRNA-seq) transcriptomics and adopted the Query method and the Overlap method to determine cell type enrichments in histopathological regions. Distinct fibroblast cell types are highly associated with fibroblast foci, and transitional alveolar type 2 and aberrant KRT5-/KRT17+ epithelial cells are associated with morphologically normal alveoli in human IPF lungs. Furthermore, we employed laser capture microdissection directed mass spectrometry to profile proteins. By comparing with another published similar dataset, common differentially expressed proteins and enriched pathways related to ECM structure organization and collagen processing were identified in fibroblast foci. Importantly, cell type enrichment results from innovative spatial proteomics and scRNA-seq data integration accord with those from spatial transcriptomics and scRNA-seq data integration, supporting the capability and versatility of the entire approach. In summary, we integrated spatial multi-omics with scRNA-seq data to identify disease-associated cell types and potential targets for novel therapies in IPF intervention. The approach can be further applied to other disease areas characterized by spatial heterogeneity.
2025-01-27 | PXD058805 | Pride
Project description:In humans, the lacrimal gland produces the aqueous component of the tear film, which e.g. moistens and nourishes the ocular surface to maintain ophthalmic health. Decreased production of the aqueous component leads to the development of dry eye disease, which affects over 250 million people worldwide. Despite the impact on patients, the availability of primary human material to study underlying disease mechanisms is severely constrained. Here, we report the development of an immortalized human lacrimal gland epithelial cell line that improves accessibility to study the molecular pathogenesis-mechanisms of dry eye disease and link them to causal treatments.
2024-04-17 | GSE239464 | GEO
Project description:Cardiac resident macrophages (CRMs) have key roles in progression and prevention of cardiac fibrosis. We have previously shown CRMs are a genetically diverse and heterogenous cell population. Using single-cell RNA sequencing we identified a CRM subset with high expression of Chemokine (C-C motif) ligand 24 (CCL24). In this study, we uncover a profibrotic role for CCL24 through fibroblast activation and regulation of ECM pathways.
2025-09-17 | GSE300219 | GEO