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Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): synthetic construct Mus musculus

PROVIDER: GSE111323 | GEO | 2018/04/05

REPOSITORIES: GEO

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Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration.

Project description:Macrophage aging is pathogenic in diseases of the elderly, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. However, the role of microRNAs, which modulate immune processes, in regulating macrophage dysfunction and thereby promoting age-associated diseases is underexplored. Here, we report that microRNA-150 (miR-150) coordinates transcriptomic changes in aged murine macrophages, especially those associated with aberrant lipid trafficking and metabolism in AMD pathogenesis. Molecular profiling confirmed that aged murine macrophages exhibit dysregulated ceramide and phospholipid profiles compared with young macrophages. Of translational relevance, upregulation of miR-150 in human peripheral blood mononuclear cells was also significantly associated with increased odds of AMD, even after controlling for age. Mechanistically, miR-150 directly targets stearoyl-CoA desaturase-2, which coordinates macrophage-mediated inflammation and pathologic angiogenesis, as seen in AMD, in a VEGF-independent manner. Together, our results implicate miR-150 as pathogenic in AMD and provide potentially novel molecular insights into diseases of aging.

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Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration: part II

Project description:We identified that microRNA-150 is upregulated in aged macrophages of diverse origins and therefore may mechanistically skew them towards a disease-promoting phenotype. The purpose of this experiment was to identify how the murine transcriptome changes with microRNA-150 overexpression.

2018-04-05 | GSE111322 | GEO

Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration: part I

Project description:Macrophage aging is pathogenic in numerous age-associated diseases, including age-related macular degeneration. The purpose of this experiment was to profile microRNA expression in young and aged macrophages at baseline and in response to oxLDL and acLDL.

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Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration

Project description:Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration

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Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration: part II

Project description:Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration: part II

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Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration: part I

Project description:Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration: part I

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Natural killer cells cooperate with neutrophils to suppress pathological angiogenesis in neovascular age-related macular degeneration

Project description:Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population associated with focal inflammation, however, understanding of the precise immune components governing this process is still limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions. O-link analysis and single-cell RNA sequencing approaches identified CCR5-expressing NK cells is essential for further NK cell recruitment and extravasation in CNV site. NK cells suppress pathological angiogenesis via through clearance of senescent vasculatures, a process that requires neutrophil extracellular traps (NETs). Mechanistically, the release of NETs results from NKG2D-dependent NK cell activation and production of IFN-γ at CNV lesions. Notably , age is the strongest risk factor for AMD to an aged immune system; our human and mouse data showed that aged NK cells exhibited compromised protective effects. Additionally, expansion of NK cells by IL-2 complex improved CNV formation. Collectively, our results revealed a previously unrecognized role of NK cells in suppressing nvAMD progression, suggesting these cells as a potential target for future immune therapies for patients with nvAMD.

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Natural killer cells cooperate with neutrophils to suppress pathological angiogenesis in neovascular age-related macular degeneration [scRNA-seq]

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Project description:This study explored the expression of several miRNAs reported to be deregulated in age-related macular degeneration (AMD). Total RNA was isolated from sera from patients with dry AMD (n = 12), wet AMD (n = 14), and controls (n = 10). Forty-two previously investigated miRNAs were selected based on published data and their role in AMD pathogenesis, such as angiogenic and inflammatory effects, and were co-analysed using a miRCURY LNA miRNA SYBR® Green PCR kit via quantitative real-time polymerase chain reaction (qRT-PCR) to validate their presence. Unsupervised hierarchical clustering indicated that AMD serum specimens have a different miRNA profile to healthy controls. We successfully validated the differentially regulated miRNAs in serum from AMD patients versus controls. Eight miRNAs (hsa-let-7a-5p, hsa-let-7d-5p, hsa-miR-23a-3p, hsa-miR-301a-3p, hsa-miR-361-5p, hsa-miR-27b-3p, hsa-miR-874-3p, hsa-miR-19b-1-5p) showed higher expression in the serum of dry AMD patients than wet AMD patients and compared with healthy controls. Increased quantities of certain miRNAs in the serum of AMD patients indicate that these miRNAs could potentially serve as diagnostic AMD biomarkers and might be used as future AMD treatment targets. The discovery of significant serum miRNA biomarkers in AMD patients would provide an easy screening tool for at-risk populations.

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Age-related macular degeneration.

Project description:CLINICAL QUESTION:Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? RESULTS:We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. IMPLEMENTATION:strategy of administration, safety of intravitreal injection.

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