Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression data from GFP- or GFP Satellite alpha-transfected human retinal pigment epithelia cell line ARPE19

ABSTRACT: Oxidative stress (OS) and inflammation play pivotal roles in retinal pigment epithelium (RPE) degeneration and age-related macular degeneration (AMD) pathogenesis. Interleukin 17 (IL17) signaling is a founding pathway regulating inflammatory response, the IL17 ligand has been shown to induce RPE degeneration and is emerging as a potential target for AMD treatment. However, the regulation and function of IL17 receptors are largely unexplored in RPE cells under OS. Here, we identified that IL17RA was significantly upregulated in the presence of OS both in human and mouse RPE cells. We found that OS upregulates expression of reprogramming factor Kruppel-like factor 4 (KLF4), which directly binds to the IL17RA promoter and activates IL17RA transcription, therefore inducing RPE proinflammatory response. Furthermore, our results reveal that KLF4 isoform 2, but not the canonical KLF4 isoform1, is the major isoform in RPE cells that activates IL17RA transcription. Finally, we demonstrate that mRNA level of IL17RA was positively correlated with that of KLF4 isoform2 in AMD patients. Together, our data demonstrates a new regulatory mechanism of IL17RA by KLF4 upon OS exposure, which is likely to play a role in AMD pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122270 | GEO | 2018/11/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Microglia-RPE Cell Communication via the SPP1-ITGAV Axis Drives EMT and Retinal Degeneration in Dry AMD

Project description:Age-related macular degeneration (AMD) is a leading cause of vision loss, with its dry form characterized by retinal pigment epithelium (RPE) degeneration and photoreceptor loss. However, the underlying mechanisms driving these pathological changes remain poorly understood. Here, we identify a critical role for microglia-RPE cell interactions mediated by the SPP1-ITGAV signaling axis in dry AMD pathogenesis.

2024-11-12 | GSE281280 | GEO

Functional Retinal Pigment Epithelium-like Cells from Human Fibroblasts

Project description:The retinal pigment epithelium (RPE) provides vital support to photoreceptor cells and its dysfunction is associated with the onset and progression of age-related macular degeneration (AMD). Surgical provision of RPE cells may ameliorate AMD and thus it would be valuable to develop sources of patient-matched RPE cells for this application of regenerative medicine. We describe here the generation of functional RPE-like cells from fibroblasts that represent an important step toward that goal. We identified candidate master transcriptional regulators of RPEs using a novel computational method and then used these regulators to guide exploration of the transcriptional regulatory circuitry of RPE cells and to reprogram human fibroblasts into RPE-like cells. The RPE-like cells share key features with RPEs derived from healthy individuals, including morphology, gene expression and function, and thus represent a step toward the goal of generating patient-matched RPE cells for treatment of macular degeneration. Expression analysis was performed on induced retinal pigment epithelium-like cells.

2015-09-23 | E-GEOD-64264 | biostudies-arrayexpress

DARPP32, a target of hyperactive mTORC1 in the retinal pigment epithelium

Project description:The mechanistic target of rapamycin (mTOR) is assembled into signaling complexes of mTORC1 or mTORC2, and plays key roles in cell metabolism, stress response, nutrient and growth factor sensing. Accumulating evidence from human and animal model studies has demonstrated a pathogenic role of hyperactive mTORC1 in age-related macular degeneration (AMD). The retinal pigment epithelium (RPE) is a primary injury site in AMD. In mouse models of RPE-specific deletion of Tuberous sclerosis 1 (Tsc1), which encodes an upstream suppressor of mTORC1, the hyperactivated mTORC1 metabolically reprogrammed the RPE and led to the degeneration of the outer retina and choroid (CH). In the current study, we used single-cell RNA sequencing (scRNA-seq) to identify a novel RPE mTORC1 downstream protein, dopamine and cyclic AMP-regulated phosphoprotein of molecular weight 32,000 (DARPP-32). DARPP-32 was not found in healthy RPE but localized to drusen and basal linear deposits in human AMD eyes. In animal models, overexpressing DARPP-32 by adeno-associated virus (AAV) led to abnormal RPE structure and function. The data indicate that DARPP-32 is a previously unidentified signaling protein subjected to mTORC1 regulation and may contribute to RPE degeneration in AMD.

2022-07-29 | GSE209908 | GEO

Feedback regulation between ALKBH3-mediated glycolysis and histone lactylation promotes age-related macular degeneration

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

Large-Scale Quantitative Proteomics of Retinal Mitochondrial Fractions from Age-Related Macular Degeneration (AMD) Patients

Project description:Age-related macular degeneration (AMD) is the leading cause of blindness in seniors, with no effective treatment options available for most patients. AMD is characterized by the death of retinal pigment epithelium (RPE) and photoreceptors, resulting in central vision loss causing tremendous difficulties in performing daily tasks requiring visualization of fine details visualization. Dysfunction of RPE mitochondria is a critical early event involved in AMD pathogenesis, and we previously reported that maintaining normal mitochondrial functions in RPE could be a viable option for AMD treatment. We hypothesize that dysregulation of RPE mitochondrial proteome is highly relevant to the loss of RPE mitochondrial function during the transition from healthy aging to early AMD. The hypothesis was examined by quantitative proteomics using UHR-IonStar.

2022-07-13 | PXD033413 | Pride

A widespread decrease of chromatin accessibility in age-related macular degeneration

Project description:Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. The extent to which epigenetic changes regulate the progression of AMD is unclear. Here we profiled chromatin accessibility in the retina and retinal pigmented epithelium (RPE) from AMD patients and controls. Global decreases in chromatin accessibility occur in the RPE in early AMD and in the retina with advanced disease. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs) and reduced AMD. Genes associated with DARs show altered expression in AMD. Cigarette smoke, an established risk factor for AMD, applied to human iPSC-derived RPE cells recapitulates epigenomic changes seen in AMD. In addition to providing a comprehensive profile of chromatin accessibility in human RPE and retina, this study shows that global decreases in chromatin accessibility may play a critical role in AMD progression.

2018-03-05 | GSE99287 | GEO

Non-canonical roles of CFH in retinal pigment epithelial cells revealed by dysfunctional rare CFH variants

Project description:Complement Factor H (CFH) common genetic variants have been associated with age-related macular degeneration (AMD). While most previous in vitro RPE studies focused on the common p.His402Tyr CFH variant, we characterized rare CFH variants that are highly penetrant for AMD using induced pluripotent stem cell derived retinal pigment epithelium (iPSC-RPE). Our results show that lower FH levels were detected in AMD RPE, which potentially disrupted canonical and non-canonical roles of FH. Specifically, AMD RPE displayed higher inflammation rate and a reduced set of differentially expressed genes compared to control RPE upon A2E and blue light challenge. Additionally, cholesterol efflux and POS phagocytosis defects, dysregulated complement levels, larger sub-RPE deposits and increased mitochondrial stress were observed in AMD RPE. Thus, our study reveals new non-canonical roles for FH in regulating important RPE functions.

2024-12-02 | GSE275494 | GEO

The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in non-neovascular AMD

Project description:Non-neovascular or dry age-related macular degeneration (AMD) is a multi-factorial disease with degeneration of the aging retinal-pigmented epithelium (RPE) as a central pathogenic driver. Lysosomes play a crucial role in RPE health due to their involvement in phagocytosis and autophagy, which are regulated by transcription factor EB/E3 (TFEB/E3). Disruption in these processes can accelerate aging disorders, like AMD. Here we tried to ascertain if upregulation of AKT2 in the RPE cells triggers abnormalities lysosomal/autophagy processes and mitochondrial function culminating into an early AMD-like phenotype using mouse and in vitro "disease in a dish" models as tools.

2024-06-14 | GSE269923 | GEO

Retinal pigment epithelium extracellular vesicles are potent inducers of age-related macular degeneration disease phenotype in the outer retina

Project description:Age-related macular degeneration (AMD) is a leading cause of blindness. Vision loss is caused by the loss of the retinal pigment epithelium (RPE) and photoreceptors and/or retinal and choroidal angiogenesis. Here we use AMD patient specific RPE cells with the Y402H high-risk polymorphism in the complement factor H to perform a comprehensive analysis of EVs, their cargo and role in disease pathology. We show that AMD RPE is characterised by enhanced and polarised EV secretion. Transcriptomic, proteomic and lipidomic analyses demonstrate that AMD RPE EVs carry RNA, proteins and lipids that reflect changes in the parental RPE and mediate key AMD pathological processes including oxidative stress, cytoskeletal dysfunction, angiogenesis and drusen accumulation. We demonstrate that exposure of control RPE to AMD RPE apical EVs leads to the formation of stress vacuoles, cytoskeletal destabilization, and abnormalities in the morphology of the nucleus in the recipient cells. Treatment of retinal organoids with apical AMD RPE EVs leads to disrupted neuroepithelium and appearance of cytoprotective alpha B crystallin immunopositive cells, with some co-expressing retinal progenitor cell markers Pax6 or Vsx2, suggesting activation of regenerative pathways upon injury. These findings indicate that AMD RPE EVs mediated signalling have an important role in disease progression.

2022-01-21 | MSV000088713 | MassIVE

Epithelial phenotype restoring drugs suppress macular 1 degeneration phenotypes in an iPSC model

Project description:Age-related Macular Degeneration (AMD), a blinding eye disease, is characterized by pathological protein- and lipid-rich drusen deposits underneath the retinal pigment epithelium (RPE) and atrophy of the RPE monolayer in advanced disease stages - leading to photoreceptor cell death and vision loss. Currently, there are no drugs to stop drusen formation or RPE atrophy in AMD. We developed an iPSC-RPE AMD model that recapitulates drusen and RPE atrophy. Drusen deposition is dependent on AMD-risk-allele CFH(H/H) and anaphylatoxin triggered alternate complement signaling via the activation of NF-B and downregulation of autophagy pathways. High-throughput screen identified two drugs, L-745,870, a dopamine receptor antagonist, and aminocaproic acid, a protease inhibitor that reduce drusen deposits and restore RPE epithelial phenotype in anaphylatoxin challenged iPSC-RPE with or without the CFH(H/H) genotype. This comprehensive iPSC-RPE model replicates key AMD phenotypes, provides molecular insight into the role of CFH(H/H) risk-allele in AMD, and discovers two candidate drugs to treat AMD.

2021-10-12 | GSE185310 | GEO

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