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Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy [scRNA-seq]

ABSTRACT: Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy [scRNA-seq]

PROVIDER: PRJNA857703 | ENA |

REPOSITORIES: ENA

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Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy [scRNA-seq]

Project description:Glaucoma is an optic neuropathy characterized by progressive degeneration of retinal ganglion cells (RGCs) and visual loss. Previous studies have reported that the variation of the ATP-binding cassette transporter 1 (ABCA1) gene is linked to a higher risk of glaucoma in humans, but the pathological mechanisms remain unknown. Here we report that ABCA1 loss, especially in astrocytes, causes optic neuropathy. ABCA1 was mainly expressed in astrocytes rather than neurons, and that knockout of Abca1 gene under GFAP promoter (Glia-KO) caused age-associated RGC degeneration and ocular dysfunction without affecting intraocular pressure, a major risk factor for glaucoma. Glia-KO mice showed age-associated changes in astrocyte reactivity accompanied by the accumulation of cholesterol, a major substrate of ABCA1. Single-cell RNA sequencing revealed that Abca1 deficiency causes astrocyte-triggered inflammation and increased sensitivity of RGCs against excitotoxicity. Altogether, these findings suggest that astrocytic dysfunction caused by ABCA1 loss triggers age-associated optic neuropathy-like pathology.

2022-07-11 | GSE207929 | GEO

Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy [bulkRNA-seq]

2022-07-11 | GSE207928 | GEO

Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy

Project description:Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy

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Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy [bulkRNA-seq]

Project description:Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy [bulkRNA-seq]

| PRJNA857704 | ENA

Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy

Project description:This SuperSeries is composed of the SubSeries listed below.

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Mitochondrial transfer of the mutant human ND6T14484C gene causes visual loss and optic neuropathy

Project description:In this study we investigated the effects of mutant human ND6 on mouse optic nerves

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Mitochondrial transfer of the mutant human ND6T14484C gene causes visual loss and optic neuropathy

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Project description:C57Bl/6J Mice were exposed to sonication to induce a traumatic optic neuropathy model. Optic nerves were harvested and mitochondrial isolation was performed. Lipids were then extracted from isolated mitochondria. Mass spectrometry was used to analyze mitochondrial lipids.

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Project description:The genetic defects leading to optic atrophy range from mitochondrial DNA (mtDNA) point mutations in LeberÃ¢Â€Â™s hereditary optic neuropathy (LHON), to dominant and recessive mutations affecting a cluster of nuclear genes implicated in mitochondrial dynamics. We performed WES in patients with an optic atrophy spectrum disorder, including retinal macular dystrophy and kidney insufficiency leading to transplantation, associated with mitochondrial DNA (mtDNA) depletion without accumulation of multiple deletions, to identify the genetic causes of this syndrome.

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The proteome of human retrobulbar optic nerve

Project description:The optic nerve is a white matter tract that conveys visual information to the brain. A detailed investigation of the proteome of the normal human retrobulbar optic nerve may help facilitate studies of the biology and pathophysiology of the optic nerve. We conducted an in-depth proteomic analysis of optic nerve from five adults. Proteins were fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. We identified 2,711 non-redundant proteins in the human retrobulbar optic nerve, including the astrocytic marker glial fibrillary acidic protein, several proteins expressed by oligodendrocytes (laminin, proteolipid protein, and fibronectin), myelin proteins (myelin basic protein, myelin-associated glycoprotein), paranodal structural proteins (neurofascin, contactin, α, β, and γ adducins, septin 2, endophilin, ankyrin β, spectrin), proteins involved in neuronal protection and regeneration (α crytallins A and B, dedicator of cytokinesis proteins, ciliary neurotrophic factor), proteins associated with open-angle glaucoma (thioredoxin, heat shock protein-70), and proteins associated with optic neuritis (aquaporin-4). Twenty-one unambiguous protein isoforms were identified in the optic nerve.

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