Effects of selective elimination of senescent cells on RPE/choroid complex in mice with subretinal drusenoid deposits
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ABSTRACT:
PROVIDER: PRJNA982173 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24887237_1.fastq.gz | Fastqsanger.gz | |||
| SRR24887237_2.fastq.gz | Fastqsanger.gz | |||
| SRR24887238_1.fastq.gz | Fastqsanger.gz | |||
| SRR24887238_2.fastq.gz | Fastqsanger.gz | |||
| SRR24887239_1.fastq.gz | Fastqsanger.gz |
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Project description:The target deletion of ATP binding cassette subfamily member 1 (ABCA1) and G1 (ABCG1) in myeloid cells leads to subretinal drusenoid deposits in mice (Abca1/g1 -m/-m). We here report the selective elimination of p16-positive cells results in the significant eduction in myeloid markers, pro-inflammatory cytokines and prostaglandin biosynthetic enzymes.
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Project description:Macular subretinal fibrosis is the end-stage complication of neovascular age-related macular degeneration (nAMD). RPE/Choroid from control and subretinal fibrosis mice were collected and processed for RNA sequencing (RNA-seq) analysis to investigate the molecular mechanism of subretinal fibrosis.
2022-04-13 | GSE189555 | GEO
Project description:Subretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). We found that overexpression of CPT1A in the RPE of Vldlr-/- mice suppresses epithelial-to-mesenchymal transition and fibrosis. Mechanistically, TGFβ2 induces fibrosis by activating a Warburg-like effect, i.e. increased glycolysis and decreased mitochondrial respiration through ERK-dependent CPT1A degradation. Moreover, VLDLR blocks the formation of the TGFβ receptor I/II complex by interacting with unglycosylated TGFβ receptor II. In conclusion, VLDLR suppresses fibrosis by attenuating TGFβ2-induced metabolic reprogramming, and CPT1A is a potential target for treating subretinal fibrosis.
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Project description:Human retina and RPE/choroid from healthy and age-related macular degeneration donors
2024-01-18 | GSE230348 | GEO
Project description:PURPOSE To identify retinal pigment epithelial (RPE)/choroid genes and their relevant expression pathways affected by intravitreal injections of dexamethasone and triamcinolone acetonide in mice at clinically relevant time points for patient care. METHODS Differential gene expression of over 34,000 well-characterized mouse genes, in the RPE/choroid of 6 week old C57BL/6J mice were analyzed after intravitreal steroid injections at 1 week and 1 month post injection, using Affymetrix Mouse Genome 430 2.0 microarrays. The data were analyzed using GeneSpringGX12.5 and Ingenuity Pathway Analysis (IPA) microarray analysis software for biologically relevant changes. RESULTS Both triamcinolone and dexamethasone caused differential activation of genes involved in âCircadian Rhythm Signalingâ pathway at both time points tested. Triamcinolone (TAA) uniquely induced significant changes in gene expression in âCalcium Signalingâ (1 week) and âGlutamate Signalingâ pathways (1month). In contrast, Dexamethasone (Dex) affected the âGABA Receptor Signalingâ (1 week) and âSerotonin Receptor Signalingâ (1month) pathways. CONCLUSIONS Understanding how intraocular steroids affect the gene expression of RPE/choroid is clinically relevant. This in vivo study has elucidated several genes and pathways that are potentially altering the circadian rhythms and several other neurotransmitter pathways in RPE/choroid cells during intravitreal steroid injections, which likely has consequences in the dysregulation of RPE function and neurodegeneration of the retina. Total of 18 RPE/choroid samples were analysed. There were two time points, day7 and day30. Each time point had three groups: BSS control, DEX treatment and TAA treatment. Each group had three biological replicas.
2016-08-01 | E-GEOD-49872 | biostudies-arrayexpress
Project description:To characterize underlying changes in the retinal pigment epithelium (RPE)/choroid with age, we produced gene expression profiles for the RPE/choroid and compared the transcriptional profiles of the RPE/choroid from young and old mice. The changes in the aged RPE/choroid suggest that the tissue has become immunologically active. Such phenotypic changes in the normal aged RPE/choroid may provide a background for the development of age-related macular degeneration. Experiment Overall Design: We compared the gene expression of retinal pigmental epithelium/choroid from young and old animals. There were 4 samples from young mice and 4 samples from old mice. Each sample contained 4 retinal pigmental epithelium/choroid from 2 animals
2008-06-11 | E-GEOD-10965 | biostudies-arrayexpress
Project description:<p>Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes. </p> <p>Reprinted from <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=25446321">Whitmore, S.S., Wagner, A.H., DeLuca, A.P., Drack, A.V., Stone, E.M., Tucker, B.A., Zeng, S., Braun, T.A., Mullins, R.F., Scheetz, T.E., 2014. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq. Experimental Eye Research</a>. Used under <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported </a>license.</p> <p>Additional RNA sequencing was performed on temporal, macular, nasal, inferior, and superior retina from a fifth subject and is included in this dataset. See original publication for details.</p>
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Project description:Single nuclei RNA sequencing identified choroidal endothelial cells and fibroblasts as the primary cell types responsible for increasing G-CSF expression in response to mCRP in RPE-choroid organ cultures.
2024-12-19 | GSE278749 | GEO
Project description:Purpose To examine how circulating immune mediators in vivo may affect gene and protein expression at the retinal pigment epithelium (RPE)/choroid interface. Methods Young mice were systemically infected with lymphocytic choriomeningitis virus (LCMV) or continuously infused with interferon (IFN)γ. RPE/choroid was isolated and analyzed with whole-transcriptome gene expression microarrays. Selected gene expression findings were validated at the protein level. Results Both the systemic immune activation from virus infection and the sterile systemically increased level of IFNγ resulted in increased expression of chemokine ligands, chemokine receptors and early complement components in isolates of RPE/choroid. These findings were largely absent from LCMV-infected mice deficient in either the interferon α/β receptor or IFNγ. Conclusions Together, these findings demonstrate that acute systemic immune activation results in a local response at the RPE/choroid interface that may include chemokine-dependent recruitment of inflammatory cells and engagement of the complement system. This may represent a link between the systemic low-grade inflammation and the retinal pathology observed in several multifactorial entities such as aging, age-related macular degeneration (AMD) and diabetes.
2018-12-31 | GSE73519 | GEO
Project description:Transplantation of stem cell derived retinal pigment epithelial (RPE) cells can potentially restore vision in patients with age-related macular degeneration (AMD). Several landmark Phase I/II clinical trials have demonstrated safety and tolerability of RPE transplants in AMD patients, albeit with limited efficacy. Currently, there is limited understanding of how the recipient retina regulates the survival, maturation and fate specification of transplanted RPE cells. To address this, we transplanted stem cell derived RPE into the subretinal space of immunocompetent rabbits for one month and conducted single-cell RNA sequencing analyses on the explanted RPE monolayers, compared to their age-matched in vitro counterparts. We observed an unequivocal retention of RPE identity, and a trajectory inferred survival of all in vitro RPE populations after transplantation. Furthermore, there was a unidirectional maturation trajectory towards the native adult human RPE state in all transplanted RPE cells, regardless of stem cell resource. Using adult human RPE cells as a reference, we reconstructed the gene regulatory networks in our transplanted stem cell derived RPE, and identified tripartite transcription factors (MAFF, JUND and FOS), known to modulate a broad array of RPE functions in vivo. This includes regulation of canonical RPE signature genes known to support host photoreceptors, and pro-survival genes required for adaptation to the host subretinal microenvironment. These findings shed insights into the transcriptional landscape of RPE cells after subretinal transplantation, with important implications for cell-based therapy for AMD.
2023-05-22 | GSE212896 | GEO