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Metabolic reprogramming of the neovascular niche promotes regenerative angiogenesis in proliferative retinopathy

ABSTRACT: Metabolic reprogramming of the neovascular niche promotes regenerative angiogenesis in proliferative retinopathy

PROVIDER: PRJNA894955 | ENA |

REPOSITORIES: ENA

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Metabolic reprogramming of the neovascular niche promotes regenerative angiogenesis in proliferative retinopathy

Project description:Healthy blood vessels supply neurons to preserve metabolic function. In blinding proliferative retinopathies (PRs), pathological neovascular tufts often emerge in lieu of needed physiological revascularization. Here we show that metabolic shifts in the neovascular niche define angiogenic fate. Fatty acid oxidation (FAO) metabolites accumulated in human and murine retinopathy samples. Neovascular tufts with a distinct single-cell transcriptional signature highly expressed FAO enzymes. The deletion of Sirt3, an FAO regulator, shifted the neovascular niche metabolism from FAO to glycolysis and suppressed tuft formation. This metabolic transition increased Vegf expression in astrocytes and reprogrammed pathological neovessels to a physiological phenotype, hastening vascular regeneration of the ischemic retina and improving vision. Hence, strategies to change the metabolic environment of vessels could promote a regenerative phenotype in vascular diseases.

2025-04-01 | GSE216676 | GEO

Induced Expression of VEGFC, ANGPT, and EFNB2 and Their Receptors Characterizes Neovascularization in Proliferative Diabetic Retinopathy

Project description:Proliferative diabetic retinopathy (PDR) is the advanced stage of diabetic retinopathy (DR), coupling with irregular neovascularization, and is the leading cause of blindness in working-age people; but the molecular mechanism of vascular differentiation in PDR remains poorly characterized. In our study, we obtained the transcriptome profile of neovascular proliferative membrane specimens from patients with PDR via high-throughput sequencing and advanced bioinformatics. Marker genes of neovascularization were validated and distinct gene expression patterns were formed of PDR compared with normal retina. We also discovered gene sets that were co-expressed with vascular endothelial growth factor A (VEGFA), including transcription factors (TFs) that dysregulate VEGFA. In particular, ETS transcription factors family could negatively regulate VEGFA. We also detected a set of genes related to PDR was dramatically changed from pre-mRNA to mature mRNA. In summary, our study firstly presented the profile of neovascular proliferative membrane and identified new marker genes and key regulators of VEGFA, which could contribute the molecular therapy of PDR in the future.

2020-08-10 | GSE102485 | GEO

Vitreous of proliferative diabetic retinopathy patients

Project description:Vitreous of proliferative diabetic retinopathy patients

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gut microbiome of proliferative diabetic retinopathy

Project description:gut microbiome of proliferative diabetic retinopathy Metagenome

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RNA-sequencing of the oxygen induced retinopathy (OIR) model in C57BL/6 mice

Project description:Pathological retinal angiogenesis is one of the major causes of vision loss worldwide. The breakdown of blood vessels and aberrant vessels growth usually lead to hemorrhage, macular edema, fibrotic scar, and retinal detachment. OIR model serves as a proxy for human pathological retinal neovascularization such as proliferative diabetic retinopathy, retinal vein occlusion and retinopathy of prematurity. C57BL/6 mice were exposed to 75% O2 in a hyperoxic chamber from postnatal day P7 to P12 and then returned to room air. The greatest neovascular response occurred at postnatal 17 days (P17) when the mice are put back to room air condition for 5 days. In order to reveal potential genes that involve in pathological neovascularization, we performed transcriptomic analyses of retina of P17.

2024-08-20 | GSE241239 | GEO

Expressing profiles of small non-coding RNA in mouse models of oxygen-induced retinopathy (OIR)

Project description:Pathologic ocular angiogenesis is a common cause of blindness in proliferative retinopathy. Small non-coding RNAs (sncRNAs) play critical roles in normal development and diseases, and their function in eye diseases and angiogenesis are increasingly recognized. In the present study, we aimed to identify the function and therapeutic potential of sncRNAs in retinopathy. We used microarray to analyze the retinal expression profile of sncRNAs in a mouse oxygen-induced retinopathy (OIR) model that mimic human proliferative retinopathy.

2017-02-10 | GSE84303 | GEO

In-depth molecular characterization of neovascular membranes suggests a role for hyalocytes-to-myofibroblasts transdifferentiation in proliferative diabetic retinopathy

Project description:In-depth molecular characterization of neovascular membranes suggests a role for hyalocytes-to-myofibroblasts transdifferentiation in proliferative diabetic retinopathy

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BGN stimulates retinal pathological angiogenesis via up-regulation of CXCL12 expression in pericytes (mouse)

Project description:Retinal pathological angiogenesis (PA) is a common hallmark in proliferative retinopathies, including age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR), and retinopathy of prematurity (ROP). The mechanisms underlying PA is complex and incompletely understood. Using oxygen-induced retinopathy (OIR) mouse as a model, the role of extracellular matrix (ECM) protein biglycan (BGN) in PA was studied. Significant upregulation of BGN in the retina of OIR mice and in neovascular proliferative membranes of PDR patients was found. The reduction of BGN expression by Bgn-specific small interfering RNA (siRNA) effectively diminished retinal PA in OIR mouse. Subsequent analysis of the mouse OIR retinal single-cell RNA sequencing data from the Gene Expression Omnibus dataset (GSE150703) suggested pericyte as a source of BGN. This was verified using cultured retinal capillary pericytes. BGN expression in pericytes was highly sensitive to hypoxic stimulation. BGN stimulated retinal PA via the upregulation of C-X-C motif chemokine ligand 12 (CXCL12). Inhibition of the CXCL12-CXCR4 axis effectively diminished PA in OIR mouse. In conclusion, this study demonstrated the stimulatory role of BGN in retinal PA, identified the link between BGN and CXCL12 expression, and further highlighted the role of pericytes in retinal PA.

2025-02-10 | GSE259255 | GEO

BGN stimulates retinal pathological angiogenesis via up-regulation of CXCL12 expression in pericytes (human)

2025-02-10 | GSE259254 | GEO

Vitreous of proliferative diabetic retinopathy patients

Project description:We identified lncRNA expression profiles in vitreous samples between proliferative diabetic retinopathy (PDR) patients and idiopathic macular hole (IMH) patients, and between PDR patients who had received preoperative anti-vascular endothelial growth factor (anti-VEGF) therapy and PDR patients who had received surgery alone. There had been the systemic expression differences in vitreous at the microarray level from PDR patients and IMH patients, and from PDR patients after anti-VEGF treatment and untreated PDR patients.

2022-07-15 | GSE191210 | GEO

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