Transcriptional Comparison of Human and Murine Retinal Neovascularization
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PROVIDER: PRJNA981457 | ENA |
REPOSITORIES: ENA
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Project description:Background: Retinal neovascularization (RNV) as a result of retinal ischemia, such as in proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP), can lead to vitreous hemorrhage, tractional retinal detachment, and irreversible loss of vision if left untreated. Although panretinal laser photocoagulation and anti-vascular endothelial growth factor (VEGF) injections are efficient treatment modalities, a significant number of patients do not respond to either treatment. This clinical finding suggests that other, previously unrecognized mediators and signaling pathways may contribute to RNV development and could represent valuable targets for future treatments. Methods: In search of phylogenetically conserved angiogenic mediators, we examined the transcriptional profile of murine RNV from C57BL/6J mice (n=14) in the oxygen-induced retinopathy (OIR) model as well as human RNV membranes from PDR patients (n=7), who had undergone vitrectomy and compared them with corresponding control tissues (n=13, 10 respectively). Genes that were differentially expressed (DEGs) between RNV and control samples were identified for human and murine samples and their associated gene ontology (GO) clusters analyzed. Lastly, human and murine DEGs were compared to identify phylogenetically conserved factors. Findings: Transcriptional profiles of murine RNV showed that DEGs linked to the activation of the innate immune system (Msn, Cd34), extracellular matrix organisation (Col4a1, Gfap), and regulation of angiogenesis (Col4a2, Fgf2) were significantly upregulated both at the ischemic, preproliferative stage of the disease (OIR p14) as well as at the proliferative stage (OIR p17). While similar GO terms were upregulated in human RNV, only a small overlap in DEGs between both species was detected. Phylogenetically conserved mediators upregulated in both murine and human RNV included ANGPT2, S100A8, MCAM, EDNRA, MRC1, and CCR7. Interpretation: This study identifies phylogenetically conserved inflammatory and pro-angiogenic mediators that are significantly upregulated in both murine and human RNV. Among them, MCAM, ENDRA and MRC1 emerged as the most upregulated, phylogenetically conserved DEGs not yet implicated in human RNV, thus representing potential new treatment targets for ischemic retinal diseases.
2024-01-03 | GSE234447 | GEO
Project description:In order to find out the vital genes during retinal neovascularization (RNV), we set up OIR (oxygen-induced retinopathy; induced with 75%±2% oxygen) and wild-type C57BL/6J murine models. We observed the retinal vascular growth process daily both in OIR and wild-type mice through retinal flat-mount, and isolated total retinal RNA at different time points (P8, P9, P12, P13, P30) both in OIR and wild-type mice for gene expression analysis. At least three different retinae were accessed at each time point for observing the retinal vascular growth process. Ten neural retinae from five mice were harvested and pooled into one sample for gene expression analysis. Three biological replicates were used for each time point. Dye-swaps were performed.
2012-12-05 | E-GEOD-38762 | biostudies-arrayexpress
Project description:In order to find out the vital genes during retinal neovascularization (RNV), we set up OIR (oxygen-induced retinopathy; induced with 75%±2% oxygen) and wild-type C57BL/6J murine models. We observed the retinal vascular growth process daily both in OIR and wild-type mice through retinal flat-mount, and isolated total retinal RNA at different time points (P8, P9, P12, P13, P30) both in OIR and wild-type mice for gene expression analysis.
2012-12-05 | GSE38762 | GEO
Project description:Emerging evidence suggests a link between the circadian clock and retinopathies though the causality has not been established. Circadian clocks in the mammalian retina regulate a diverse range of retinal functions that allow the retina to adapt to the light-dark cycle. We report that clock genes are expressed in the embryonic retina, and the embryonic retina requires light cues to maintain robust circadian expression of the core clock gene, Bmal1. Deletion of Bmal1 and Per2 from the retinal neurons results in retinal angiogenic defects similar to when animals are maintained under constant light conditions. Using two different models to assess pathological neovascularization, we show that neuronal Bmal1 deletion reduces neovascularization with reduced vascular leakage, suggesting that a dysregulated circadian clock primarily drives neovascularization. Chromatin immunoprecipitation sequencing analysis suggests that semaphorin signaling is the dominant pathway regulated by Bmal1. Our data indicate that therapeutic silencing of the retinal clock could be a common approach for the treatment of certain retinopathies like diabetic retinopathy and retinopathy of prematurity.
2022-07-01 | GSE207271 | GEO
Project description:Secreted phosphoprotein 1 expression in retinal mononuclear phagocytes links murine to human choroidal neovascularization
| PRJNA671602 | ENA
Project description:Neovascular age-related macular degeneration represents the most common cause of blindness in the western world. Alterations of the outer Blood-retina barrier integrity and a localized inflammatory microenvironment lead to sprouting of choroidal neovascularization in intimate contact with surrounding myeloid cells and ultimately lead to visual impairment. The discovery of novel targets interfering with angiogenesis and inflammation is vital for the future treatments in AMD patients. To identify novel potential targets in the local phagocytes of the retina, microglia, we performed a comprehensive RNA-seq analysis in the mouse model of laser-induced choroidal neovascularization (mCNV). Here, we identified the angiogenic factor Osteopontin (Opn), also known as "secreted phosphoprotein 1” (Spp1), to be one of the most highly expressed genes in retinal microglia in the course of CNV formation. We could confirm the presence of SPP1 at the lesion site in recruited retinal microglia of Cx3cr1CreER:Rosa26-Tomato reporter mice using immunohistochemistry and in whole retinal tissue lysates by ELISA compared to controls highlighting a massive local production of SPP1. Inhibition of SPP1 by intravitreal injection of anti-SPP1 antibody significantly increased the lesion size compared to IgG-treated control eyes. In line with the results in rodents, we found an increased SPP1 mRNA expression in surgically extracted human choroidal neovascular (hCNV) membranes by the quantitative RNA-seq approach of massive analysis of cDNA ends (MACE) and found numerous IBA1+SPP1+ myeloid cells in human CNV membranes. Taken together, these results highlight the importance of SPP1 in the formation of CNV and potentially offer new opportunities for therapeutic intervention by inhibiting the SPP1 pathway.
2021-02-16 | GSE160011 | GEO
Project description:A local neuronal clock regulates retinal angiogenesis and neovascularization
| PRJNA854612 | ENA
Project description:The purpose of this study is to identify disease-related miRNAs in retinas of a mouse model of oxygen-induced retinopathy (OIR). OIR pups were exposed to 75% oxygen at postnatal day (P)7 for 5 days, and were returned to room air at P12. The miRNAs expression profiles in the retinas from OIR mice at P17 and room air controls were determined through microarray analysis. Expressions of significantly upregulated and downregulated miRNAs in the OIR retinas and controls were confirmed through quantitative real-time RT-PCR (qPCR). Compared to the room air controls, 3 miRNAs were significantly up-regulated, and 8 miRNAs were down-regulated in OIR retinas. Our findings indicated that several miRNAs were differentially expressed in the oxygen-induced retinal neovascularization, which might provide novel therapeutic targets in regulating retinal neovascular diseases.
2018-06-19 | GSE115949 | GEO
Project description:Background: Retinal neovascularization (RNV) is a leading cause of blindness worldwide. Long non-coding RNA (lncRNA) and competing endogenous RNA (ceRNA) regulatory networks play vital roles in angiogenesis. The RNA-binding protein galectin-1 (Gal-1) participates in pathological RNV in oxygen-induced retinopathy mouse models. However, the molecular associations between Gal-1 and lncRNAs remain unclear. Herein, we aimed to explore the potential mechanism of action of Gal-1 as an RNA-binding protein. Results: A comprehensive network of Gal-1, ceRNAs, and neovascularization-related genes was constructed based on transcriptome chip data and bioinformatics analysis of human retinal microvascular endothelial cells. We also conducted functional enrichment and pathway enrichment analyses. Fourteen lncRNAs, twenty-nine miRNAs, and eleven differentially expressed angiogenic genes were included in the Gal-1/ceRNA network. WT1-AS, LINC01140, and LUCAT1 were situated at the center of the network. Additionally, several key angiogenic genes, such as apelin, angiomotin, and C-X-C motif chemokine ligand 10, were found to potentionally interact with Gal-1 via the ceRNA axis. Furthermore, Gal-1 may be involved in regulating biological processes related to chemotaxis, chemokine-mediated signaling, the immune response, and the inflammatory response. Conclusions: The Gal-1/ceRNA axis identified in this study may play a vital role in RNV. This study provides a foundation for the continued exploration of therapeutic targets and biomarkers associated with RNV.
2023-06-21 | GSE221037 | GEO
Project description:Expression profiling of microRNAs in oxygen-induced retinal neovascularization in mice
| PRJNA476577 | ENA