Aqueous microRNA profiling in age-related macular degeneration and polypoidal choroidal vasculopathy by next-generation sequencing
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA916689 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22926044.fastq.gz | Fastqsanger.gz | |||
| SRR22926045.fastq.gz | Fastqsanger.gz | |||
| SRR22926046.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 3 of 3 |
Similar Datasets
Project description:To investigate the roles of microRNAs in the aqueous humor of patients with typical age-related macular degeneration and polypoidal choroidal vasculopathy using next-generation sequencing.
2022-12-29 | GSE221905 | GEO
Project description:Although genome-wide association studies, animal models, and cell culture systems have yielded important insights into the pathogenesis of neovascular age-related macular degeneration (nAMD), the underlying molecular pathways remain ill defined. Recent studies have deciphered the transcriptional profile of choroidal neovascularisation (CNV) of body donor eyes and were thus limited by the time span from death to preservation and the associated rapid 5'-RNA degradation. In this study, CNVs were therefore formalin-fixed immediately after surgical extraction from patients with nAMD and analyzed using a 3’ RNA sequencing approach called Massive Analysis of cDNA Ends (MACE). Age-matched formalin-fixed paraffin-embedded (FFPE) RPE-choroidal specimens obtained from the macular region of enucleated eyes with ciliary body melanoma served as controls. Transcriptome profiles were generated and disease-associated gene signatures were identified using statistical and bioinformatic methods. Calprotectin (S100A8/A9) protein expression was investigated by immunohistochemistry and ELISA.We identified 158 differentially-expressed genes (DEG) that were significantly increased in CNV compared to control tissue. Gene ontology enrichment analysis demonstrated that these DEG contributed to biological processes, such as Blood Vessel Development, Extracellular Structure Organization, Response to Wounding and several immune-related terms. The S100 calcium-binding protein A8 (S100A8) and S100A9 emerged among the top DEG, as confirmed by immunohistochemistry on CNV tissue and protein analysis of vitreous samples from nAMD patients and controls. This study provides a high-resolution RNA-sequencing-based transcriptional signature of choroidal neovascular membranes in AMD patients and reveals S100A8/A9 as a novel biomarker and promising target for AMD-directed therapeutics and diagnostics.
2020-04-09 | GSE146887 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE28002: Gene expression of the whole mouse eye GSE28032: Epigenetic Regulation of IL17RC in Age-related Macular Degeneration (MeDIP-chip) Refer to individual Series
2011-03-22 | E-GEOD-28033 | biostudies-arrayexpress
Project description:Age-related macular degeneration (AMD) is a common, blinding disease of the elderly in which macular photoreceptor cells, retinal pigment epithelium, and choriocapillaris endothelial cells ultimately degenerate. Recent studies have found that degeneration of the choriocapillaris occurs early in this disease and that this endothelial cell dropout is concomitant with increased deposition of the complement membrane attack complex (MAC) at the choroidal endothelium. However, the impact of MAC injury to choroidal endothelial cells is poorly understood. To model this event in vitro, and to study the downstream consequences of MAC injury, endothelial cells were exposed to complement from human serum, compared to heat inactivated serum which lacks complement components. Cells exposed to complement components in human serum showed increased labeling with antibodies directed against the MAC, time and dose dependent cell death as assessed by lactate dehydrogenase assay, and increased permeability. RNA-Seq analysis following complement injury revealed increased expression of genes associated with angiogenesis including matrix metalloproteases (MMPs) 3 and 9, and VEGF-A. The MAC-induced increase in MMP9 RNA expression was validated using C5 depleted serum compared to C5 reconstitited serum. Increased levels of MMP9 were also determined using Western blot and zymography. These data suggest that, in addition to cell lysis, complement attack on choroidal endothelial cells promotes an angiogenic phenotype in surviving cells. RNA-Seq of RF/6A (cultured choroidal endothelial cells from Rhesus macaque) treated with either 50% heat-inactivated human serum ([CONTROL], n=3) or 50% normal human serum (active complement membrane attack complex [MAC], n=3)
2015-11-04 | E-GEOD-70806 | biostudies-arrayexpress
Project description:Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly. Using clinical samples and knockout mice, we reported that the m1A eraser ALKBH3 reshaped retinal metabolism to promote AMD. In retinal pigment epithelium (RPE), the dm1ACRISPR system demonstrated that ALKBH3 demethylated the glycolytic enzyme HK2 to activate anaerobic glycolysis, producing excessive lactate. The lactate promoted histone lactylation at H3K18, which in turn bound to ALKBH3 to amplify its transcription, establishing a positive feedback loop. The ALKBH3 inhibitor HUHS015 disrupted this loop, effectively mitigating RPE degeneration. Furthermore, ALKBH3 directly targeted the pro-angiogenic factor VEGFA to modulate the metabolic cross-talk between RPE and choroidal capillaries, thus promoting choroidal neovascularization (CNV). HUHS015 inhibited CNV synergistically with the anti-VEGF drug Aflibercept. Our study provides critical insights into the molecular mechanisms and metabolic events facilitating the progression from RPE degeneration to CNV in AMD, laying the groundwork for new treatments of AMD.
2024-08-14 | GSE274399 | GEO
Project description:Neovascular age-related macular degeneration (nAMD) remains a major cause of visual impairment and puts considerable burden on patients and health care systems. L-DOPA-treated Parkinson Disease (PD) patients have been shown to be partially protected from nAMD, but the mechanism remains unknown. Using murine models combining 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and laser-induced nAMD, standard PD treatment of L-DOPA/DOPA-decarboxylase inhibitor, or specific dopamine receptor inhibitors, we here demonstrate that L-DOPA treatment-induced increase of dopamine receptor D2 (DRD2) signaling inhibits choroidal neovascularization independently of MPTP-associated nigrostriatal pathway lesion. Analyzing a retrospective cohort of more than two hundred thousand nAMD patients receiving anti-VEGF treatment from the French nationwide insurance database, we show that DRD2-agonist treated (PD) patients have a significantly delayed age of onset for nAMD (81.4 (±7.0) vs 79.4 (±8.1) years old, respectively, p<0.0001) and reduced need for anti-VEGF therapies (-0.6 injections per 100 mg/day daily dose of DRD2 agonists the second year of treatment), similar to the L-DOPA treatment. While providing a mechanistic explanation for an intriguing epidemiological observation, our findings suggest that systemic DRD2 agonists might constitute an adjuvant therapy to delay and reduce the need for anti-VEGF therapy in nAMD patients.
2024-09-13 | GSE266525 | GEO
Project description:Dopamine D2 receptor activation inhibits choroidal neovascularization in Parkinson patients with age related macular degeneration.
| PRJNA1107506 | ENA
Project description:Illumina Infinium HumanMethylation450 BeadChip data from genomic DNA of retinal pigment epithelium from Age-related Macular Degeneration patients or age-matched controls.
2019-08-01 | E-MTAB-7183 | biostudies-arrayexpress
Project description:We profiled using single cell RNA sequencing the peripheral blood mononuclear cells from control patients and patients with age-related macular degeneration (AMD).
2023-10-06 | GSE222647 | GEO
Project description:Purpose: The goals of this study were to identify cell specific expression patterns of the retinal pigment epithelium (RPE) and a variety of choroidal cell types originating from the macula and the periphery of human donor eyes, with a particular emphasis on identifying expression signatures of choroidal endothelial cells. Methods: Independent libraries were prepared for macular and peripheral samples of combined RPE/choroid from seven donors in two single cell sequencing experiments. In the first experiment, 8-mm macular and peripheral punches of RPE/choroid from Donors 1-3 were digested in papain prior to cryopreservation and subsequent GEM barcoding/library construction. Donors 1-2 had no noted ophthalmologic disease documented, while Donor 3 was diagnosed with age-related macular degeneration. In the second experiment, 12-mm macular and peripheral punches of RPE/choroid from Donors 4-7 were digested in collagenase II prior to cryopreservation, CD31-magentic bead enrichment and subsequent GEM barcoding/library construction. Donors 5-7 had no noted ophthalmologic disease documented, while Donor 4 was diagnosed with age-related macular degeneration. In both experiments, libraries were sequenced on a HiSeq4000. Sequenced reads were mapped to the human genome build hg19 will CellRanger(v3.0.1) and filters removed cells likely to be doublets or cells with a high proportion of mitochondrial reads. Clustering of cells with similar expression profiles was performed with Seurat (v3.0.2). Results: In the first experiment with unenriched RPE/choroid from donors 1-3, we recovered 4,355 cells post filtering with 40,177,477 corresponding reads. A total of 2,167 cells originated from the macula and 2,168 cells originated from the periphery. A total of 11 clusters were identified, and highly enriched genes in each cluster were used to classify clusters into their presumed dominant cell type. Differential expression analysis was performed between cells of macular and peripheral origin in each cluster and between donors with and without a history of age-related macular degeneration. Results: In the second experiment with CD31-enriched RPE/choroid from donors 4-7, we recovered 14,234 cells post filtering with 135,742,297 corresponding reads. A total of 7,647 cells originated from the macula and 6,587 cells originated from the periphery. A total of 8,521 of these cells were presumed endothelial cells. A total of 13 clusters were identified, and highly enriched genes in each cluster were used to classify clusters into their presumed dominant cell type(s). Differential expression analysis was performed between cells of macular and peripheral origin in each cluster and between donors with and without a history of age-related macular degeneration. Within each of the endothelial clusters (Clusters 5-8), differential expression analysis was performed between each cluster and the remaining endothelial cells. Conclusions: This study provides a large atlas of single-cell level gene expression patterns of the human retinal pigment epithelium and choroidal cell types. We identify expression patterns of most expected choroidal cell populations and describe macular versus peripheral regional differences. We additionally identify enriched transcripts in specific cell populations in age-related macular degeneration. We characterize gene expression patterns along the choroidal vascular tree, and identify populations of arterial, capillary, and venous endothelial cells. Our results show that single-cell sequencing can be performed on human RPE/choroid after cryopreservation, and that CD31 magnetic bead enrichment can be employed to enrich for endothelial cells for single-cell sequencing.
2019-10-30 | GSE135922 | GEO