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PROVIDER: PRJNA853389 | ENA |
REPOSITORIES: ENA
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Project description:Comparative analysis of Retinal Angiogenesis during Inflammatory stage
| PRJNA854057 | ENA
Project description:Choroidal neovascularization (CNV) and the resulting retinal angiogenesis are pathological hallmarks of wet Age-related macular degeneration (AMD). The pathogenesis of CNV is not fully understood, but accumulated evidence has suggested the role of inflammation in the early stage of CNV. To better understand the molecular landscape during the early stage, we performed RNA-Seq and mass spectrometry-based proteomic analysis in the retina of the laser-induced CNV mouse model. Both transcriptomic and proteomic data showed dramatic activation of inflammatory response 3 days post photocoagulation. Integrative analysis suggested a moderate correlation between RNA-Seq and mass spec. Up-regulation of angiogenic factor, basic fibroblast growth factor-2 (Fgf-2), but not vascular endothelial growth factor (Vegf) was observed at both RNA and protein levels, highlighting Fgf-2 as a biomarker and potential therapeutic target during the early stage of CNV. In addition, enrichment analysis indicated a large overlap of inflammation-related genes and pathways at both levels. We also compared our findings with human retinal RNA-Seq data from AMD patients and controls. By using a multi-omics and comparative approach, our findings demonstrate the molecular landscape during the inflammatory stage of mouse CNV and provided new insight into the translation from the mouse model to understanding human AMD and its potential intervention and therapies.
2024-01-17 | GSE207171 | GEO
Project description:In the retinal vascular unit, direct communication between pericytes (PCs) and endothelial cells (ECs) is important for vessel stability and maintenance of the properties of the blood-retinal barrier (BRB). ECs and PCs sharing a common basement membrane throughout vasculogenesis tend to lose vessel integrity in the retina during Diabetic Retinopathy (DR). The proteins required to maintain BRB integrity and EC-PCs homeostasis may be altered or lost during the late angiogenic stage of DR. The selective dropout of microvascular cells during mild DR, later recruitment of unstable cells, and thereby retinal detachment in proliferative DR are still speculative; therefore, a comprehensive profiling of healthy retinal vasculature and fibrovascular membrane from the retina of proliferative diabetic retinopathy patients may provide clues for the seriousness of retinal detachment due to angiogenesis. This study aimed to isolate the retinal vasculature (RV) from a healthy human retina, making it more suitable for comparison with the microvascular cells of the fibrovascular membrane (FVM) from PDR patients, and to perform proteome profiling to understand the switch in BRB homeostasis due to DR. We first isolated the VT-NRC by removing the non-vascular retinal components, further the presence of microvascular cells in VT-NRC and FVM using IHC studies confirmed that the vascular components expressing both SMA and CD-34, were differentially expressed for Desmin, PDGFR- and CD-31 in a hefty proportion of FVM. Additionally, to confirm angiogenesis, both samples were subjected to ki67 expression which is significantly expressed in the FVM. Proteins were extracted, quantified, and fractionated using 1D-SDS-PAGE to analyze the proteomes of VT-NRC and FVM. After in-gel tryptic digestion, the peptides were analyzed in duplicate using LC–MS/MS on a tandem mass spectrometer. A total of 60 and 49 highly confident unique proteins were identified in VT-NRC and FVM, respectively, with 40 shared proteins. Similarly, using two-dimensional (2D) analysis, VT-NRC and FVM protein profiles were analyzed using MALDI-TOF. Out of ten differentially expressed spots, 6 and 4 highly confident proteins were identified in VT-NRC and FVM, respectively. GO analysis of the FVM protein revealed that a large percentage of the identified proteins had negative and positive regulation of angiogenesis, cell death, apoptosis, and cellular adhesion, being the most enriched molecular functions. Interaction network analysis using the SHINYGO 0.80 tool showed the involvement of SFN, YWHAZ, YWHAG, CFL1, CALM3, HRNR and PRKDC in ECM-receptor interaction, regulation of the actin skeleton, negative regulation of Angiogenesis and PI3 kinase pathway. SFN and HRNR mRNA levels were increased significantly in PBMC isolated from whole blood of DR patients compared with Type II Diabetic and Healthy control patient. Similarly, CFL1 and CALM3 mRNA levels were decreased. Controlling the expression of the differentially regulated proteins may prevent the retinal angiogenesis thereby fibrovascular membrane formation
2026-06-15 | PXD052211 | Pride
Project description:Retinal microvascularization can provide important informations to systemic vascular phenomena. The non-invasive quantitative description of the retinal vascularization is now possible by performing OCT-angiography and their image analysis software (vascular density and retinal perfusion). Systemic microvacular changes during the establishment of oncological treatment by targeted antiangiogenic therapy are little described in the literature. The objective of this pilot study is to describe the evolution of the retinal vascular density of patients with antiangiogenic drugs. In addition, the evolution of the retinal vascular density of patients on antiangiogenic drugs will study as a function of the response to the treatment and the toxicity of these treatments.
| 2382594 | ecrin-mdr-crc
Project description:Proliferative retinopathies are associated with abnormal angiogenesis that can result in visual impairment or vision loss. The tight junction complex regulates blood-retinal barrier integrity; however, its role in proliferative retinopathies is still at an early stage. Here, we employed human retinal endothelial cells (HRMVECs), and a mouse model of oxygen-induced retinopathy (OIR) to investigate the impact of IL-33 signaling on tight junction disintegration and pathological angiogenesis. Our experimental findings demonstrate that IL-33 induces ZO-1 serine/threonine phosphorylation and tight junction disruption in HRMVECs. In addition, mass-spectroscopy (MS) analysis revealed that treating of HRMVECs with IL-33 induces ZO-1 phosphorylation at Thr861 residue. Furthermore, we observed that NOX1-PKC- signaling modulates IL-33-induced ZO-1 phosphorylation and tight junction integrity in HRMVECs. We also observed that IL-33 depletion significantly reduces OIR-induced NOX1-PKC-ZO-1 signaling, vascular leakage, and pathological retinal neovascularization in the ischemic retina. We also observed that the NOX1-specific inhibitor, fluoflavine (ML-090), attenuated OIR-induced NADPH oxidase activity and pathological retinal neovascularization in the ischemic retina. Thus, we infer that IL-33-mediated NOX1-PKC-ZO-1 signaling regulates ischemia-induced retinal endothelial cell tight junction disruption and retinal neovascularization.
2025-10-14 | PXD060282 | Pride
Project description:Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is essential for the development of new organ systems, but transcriptional control of angiogenesis remains incompletely understood. Here we report that FOXC1 is essential for retinal angiogenesis. Endothelial cell (EC)-specific loss of Foxc1 impairs retinal vascular growth and expression of Slc3a2 and Slc7a5, which encode the heterodimeric CD98 (LAT1/4F2hc) amino acid transporter and regulate the intracellular transport of essential amino acids and activation of the mammalian target of rapamycin (mTOR). EC-Foxc1 deficiency diminishes mTOR activity, while administration of the mTOR agonist MHY-1485 rescues perturbed retinal angiogenesis. EC-Foxc1 expression is required for retinal revascularization and resolution of neovascular tufts in a model of oxygen-induced retinopathy. Foxc1 is also indispensable for pericytes, a critical component of the blood-retina barrier during retinal angiogenesis. Our findings establish FOXC1 as a crucial regulator of retinal vessels and identify therapeutic targets for treating retinal vascular disease.
2024-04-15 | GSE262908 | GEO
Project description:Blood vessel growth and remodelling are essential during embryonic development and disease pathogenesis. The diversity of endothelial cells (ECs) is transcriptionally evident and ECs undergo dynamic changes in gene expression during vessel growth and remodelling.Here, we investigated the role of the histone acetyltransferase HBO1 (KAT7), which is important for activating genes during development and histone H3 lysine 14 acetylation (H3K14ac). Loss of HBO1 and H3K14ac impaired developmental sprouting angiogenesis and reduced pathological EC overgrowth in the retinal endothelium. Single-cell RNA-sequencing of retinal ECs revealed an increased abundance of tip cells in Hbo1 deleted retinas, which lead to EC overcrowding in the retinal sprouting front and prevented efficient tip cell migration. We found that H3K14ac was highly abundant in the endothelial genome in both intra- and intergenic regions suggesting that the role of HBO1 is as a genome organiser that promotes efficient tip cell behaviour necessary for sprouting angiogenesis.
2021-09-30 | GSE161236 | GEO
Project description:Purpose: To investigate the role of endothelial-mesenchymal transition (EndoMT) in pathological retinal angiogenesis and identify key molecular mediators in retina angiogenesis. Methods: RNA sequencing was performed on retinal tissue from oxygen-induced retinopathy (OIR) mouse model to analyze gene expression patterns. Gene Set Enrichment Analysis was used to examine the correlation between EMT and angiogenesis gene sets. Fibronectin (FN1) expression was evaluated in endothelial cells, and its function was assessed through siRNA mediated knockdown in both in vitro angiogenesis assays and the OIR model. Results: EndoMT occurred early in retinal angiogenesis development, with significant correlation between EMT and angiogenesis gene sets. FN1 was identified as the most significantly upregulated EMT-related gene in endothelial cells. siRNA-mediated inhibition of FN1 effectively prevented VEGF-induced angiogenesis in vitro and reduced pathological angiogenesis in the OIR model. Conclusions: EndoMT is a crucial early event in pathological retinal angiogenesis, with FN1 serving as a key mediator. Targeting FN1 may provide a novel therapeutic strategy that could synergize with anti-VEGF treatments to more effectively treat pathological angiogenesis in DR and ROP, particularly in cases of poor response to anti-VEGF therapy alone.
2025-03-19 | GSE289223 | GEO
Project description:Angiogenesis, a process mediating the expansion of vascular beds in many physiological and pathological settings, requires dynamic changes in endothelial cell (EC) behavior. The molecular mechanisms governing EC activity during different phases of vascular growth, remodeling, maturation, and quiescence remain elusive. Here, we have employed actively translating transcriptome analysis of mouse retinal ECs for the characterization of dynamic gene expression changes during postnatal development and the identification of critical angiogenic factors.
2020-08-28 | E-MTAB-5087 | biostudies-arrayexpress
Project description:Müller cells play a critical role in retinal angiogenesis and inflammation, particularly in ischemic retinopathies such as oxygen-induced retinopathy (OIR). Here, we employed actively translating transcriptome profiling using RiboTag technology to selectively examine gene expression in Müller cells with and without Nrf2, a master regulator of oxidative stress responses, during OIR. Conditional deletion of Nrf2 in Müller cells exacerbated retinal avascular areas and pathological neovascularization in the OIR model, without altering Müller cell number or viability. RiboTag-based RNA sequencing and pathway analysis identified dysregulation of oxidative phosphorylation and acute phase signaling, along with suppression of pathways related to neuronal signaling. Müller cell Nrf2 deficiency resulted in dysregulation of multiple genes involved in acute-phase response, inflammation, and angiogenesis. These findings uncover a critical role for Nrf2 in maintaining Müller cell homeostasis and identify molecular signatures by which its loss amplifies retinal gliosis and pathological angiogenesis.
2025-09-18 | GSE304959 | GEO