Single-cell Transcriptomes of RPE-specific AAV-GFP/AAV-PDGF-D mouse RPE-choroid complex
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA794114 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17425667.fastq.gz | Fastqsanger.gz | |||
| SRR17425668.fastq.gz | Fastqsanger.gz | |||
| SRR17425669.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: PDGF-D is a potent angiogenic and immune-related factor. It has been demonstrated that PDGF-D play roles in the pathological process of ocular angiogenesis and degenerative diseases. In our previous study, we established a retinal pigment epithelial (RPE) cell-specifc AAV-PDGF-D/GFP mouse model to study PDGF-D's role in age-related macular degeneration (AMD). In this study, we utilized the single-cell transcriptiome seqeuncing technique to explore the cell types of immune cells attracted by PDGF-D overepxression using the same animal models, with emphases on the impact of PDGF-D overexpression on individual cell's behaviour.
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Project description:Human retina and RPE/choroid from healthy and age-related macular degeneration donors
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Project description:Wet age-related macular degeneration (AMD) is a progressive degenerative disease and a leading cause of blindness in elderly population. AMD pathogenesis initiated by several signals generates cellular and molecular cross-talk, including complement pathway-mediated inflammation, macrophage activation, and upregulation of angiogenic and cytokine/chemokine pathways. However, the mechanism by which the complement system is activated in AMD is not well understood, although its components are found in the neovascular lesions of wet AMD patients. Here, we show that increased PDGF-D expression engaged both classical and alternative complement pathways and markedly increased chemokine and cytokine responses to activate macrophages, thereby triggering neuroinflammatory milieu and exacerbating pathological neovascularization. Pharmacological targeting of the complement C3a receptor using SB290157 alleviated neuroinflammation by blocking macrophage polarization and by inhibiting pathological choroidal neovascularization (CNV). Our study thus suggests that therapeutic strategies targeting both PDGF-D and complement-mediated inflammatory signals may open up new possibilities for the treatment of neovascular diseases.
2021-06-01 | GSE164972 | GEO
Project description:High-throughput sequencing of murine retina and RPE/Choroid (eye cup) tissue following mueller-cell mediated expression of either hVEGFA, hTNFa, or hIl6 by adeno-associated viruses (AAV)
2022-11-11 | GSE200191 | 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:This is an ATAC sequencing experiment to explore chromatin accessibility change in mouse skeletal muscle treated with either AAV-GFP or AAV-CAAHR (a constitutively active mutant aryl hydrocarbon receptor). Mice received intramuscular injection of the AAV 5 months before the harvest of muscle.
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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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