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Single-cell Transcriptomic Atlas of the Human Retina Identifies Cell Types Associated with Age-Related Macular Degeneration [Microfluidics]

ABSTRACT: Single-cell Transcriptomic Atlas of the Human Retina Identifies Cell Types Associated with Age-Related Macular Degeneration [Microfluidics]

PROVIDER: PRJNA565928 | ENA |

REPOSITORIES: ENA

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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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Single-cell Transcriptomic Atlas of the Human Retina Identifies Cell Types Associated with Age-Related Macular Degeneration [Microfluidics]

Project description:Here we perform massively parallel single-cell RNA sequencing (scRNA-seq) of human retinas using two independent platforms, and report the single-cell transcriptomic atlas of the human retina. Using a multi-resolution network-based analysis, we identify all major retinal cell types, and their corresponding gene expression signatures.

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Single-cell Transcriptomic Atlas of the Human Retina Identifies Cell Types Associated with Age-Related Macular Degeneration

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Project description:Differences in regional protein expression within the human retina may explain molecular predisposition of specific regions to ophthalmic diseases like age-related macular degeneration, cystoid macular edema, retinitis pigmentosa, and diabetic retinopathy. To quantify protein levels in the human retina and identify patterns of differentially-expressed proteins, we collected foveal, macular, and peripheral retina punch biopsies from healthy donor eyes and analyzed protein content by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

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Macular Degeneration

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Single-cell Transcriptomic Atlas of the Human Retina Identifies Cell Types Associated with Age-Related Macular Degeneration [Seq-Well]

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