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Oxysterol signatures distinguish age-related macular degeneration from physiologic aging

ABSTRACT: Oxysterol signatures distinguish age-related macular degeneration from physiologic aging

PROVIDER: PRJNA436747 | ENA |

REPOSITORIES: ENA

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Oxysterol signatures distinguish age-related macular degeneration from physiologic aging

Project description:Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. The purpose of this experiment was to characterize the transcriptomic changes associated with macrophage aging.

2018-07-15 | GSE111382 | GEO

Oxysterol Signatures Distinguish Age-Related Macular Degeneration from Physiologic Aging.

Project description:Macrophage aging is pathogenic in numerous diseases, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. Although prior studies have explored the functional consequences of macrophage aging, less is known about its cellular basis or what defines the transition from physiologic aging to disease. Here, we show that despite their frequent self-renewal, macrophages from old mice exhibited numerous signs of aging, such as impaired oxidative respiration. Transcriptomic profiling of aged murine macrophages revealed dysregulation of diverse cellular pathways, especially in cholesterol homeostasis, that manifested in altered oxysterol signatures. Although the levels of numerous oxysterols in human peripheral blood mononuclear cells and plasma exhibited age-associated changes, plasma 24-hydroxycholesterol levels were specifically associated with AMD. These novel findings demonstrate that oxysterol levels can discriminate disease from physiologic aging. Furthermore, modulation of cholesterol homeostasis may be a novel strategy for treating age-associated diseases in which macrophage aging is pathogenic.

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Epigenetic Regulation of IL17RC in Age-related Macular Degeneration

Project description:This SuperSeries is composed of the following subset Series: GSE28002: Gene expression of the whole mouse eye GSE28032: Epigenetic Regulation of IL17RC in Age-related Macular Degeneration (MeDIP-chip) Refer to individual Series

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Macular Degeneration

Project description:Age-related macular degeneration has a strong epidemiological association with cardiovascular disease. One pathogenic hypothesis that applies to both diseases is the concept of an abnormal cellular response to injury resulting in a disease phenotype. It has been hypothesized that this phenotype is also present in dermal fibroblasts. This study tests this hypothesis by examination of the expression profiles of fibroblasts obtained from diseased patients and subjected to sublethal cell injury. Keywords: other

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Single-cell analysis reveals inflammatory interactions driving macular degeneration

Project description:Due to commonalities in pathophysiology, age-related macular degeneration represents a uniquely accessible model to investigate therapies for neurodegenerative diseases, leading us to examine whether pathways of disease progression are shared across neurodegenerative conditions. Here we use single-nucleus RNA sequencing to profile lesions from 17 retinas with age-related macular degeneration and controls. We create a machine learning pipeline based on recent advances in data geometry and topology and identify activated glial populations enriched in the early phase of disease. Examining single-cell data from Alzheimer’s disease and progressive multiple sclerosis with our pipeline, we find a similar glial activation profile enriched in the early phase of these neurodegenerative diseases. In late-stage age-related macular degeneration, we identify a microglia-to-astrocyte signaling axis mediated by interleukin-1beta which drives angiogenesis characteristic of disease pathogenesis. Thus, due to shared glial states, the retina provides a system for investigating therapeutic approaches in neurodegenerative diseases.

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Whole genome methylation profiling of the retinal pigment epithelium of individuals with age-related macular degeneration

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NEI CIDR Etiologic Studies of Macular Degeneration

Project description:NEI CIDR Etiologic Studies of Macular Degeneration

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Project description:NEI CIDR Etiologic Studies of Macular Degeneration

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scRNAseq of peripheral blood mononuclear cells in age-related macular degeneration

Project description:We profiled using single cell RNA sequencing the peripheral blood mononuclear cells from control patients and patients with age-related macular degeneration (AMD).

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Transcription profiling of human fibroblasts from subjects with age-related macular degeneration

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