Similar Datasets
Project description:Mitochondrial transfer of the mutant human ND6T14484C gene causes visual loss and optic neuropathy
| PRJNA622544 | ENA
Project description:PurposeTo evaluate the long-term effects of mitochondrial gene transfer of mutant human NADH ubiquinone oxidoreductase subunit VI (hND6T14484C) in the mouse eye.MethodsAdult mice were injected intravitreally with mitochondrial-targeted adeno-associated virus carrying either hND6T14484C or mitochondrial encoded mCherry. The delivery and expression of the interest gene were detected by polymerase chain reaction (PCR), quantitative PCR (qPCR), and immunostaining. The pathologic effects of the mutant gene in live mice were assessed with RNA-seq, serial spectral domain optical coherence tomography (SD-OCT), and pattern electroretinogram (PERG).ResultsDelivered hND6 was found 30-fold greater than endogenous mouse ND6 in microdissected retinal ganglion cells of hND6 -injected mice. Compared to controls injected with mCherry, PERG amplitude of hND6 mice dropped significantly at 3 (P = 0.0023), 6 (P = 0.0058), and 15 (P = 0.031) months after injection. SD-OCT revealed swelling of the optic nerve head followed by the progressive retinal and optic nerve atrophy in hND6 mice. Furthermore, RNA-seq data showed a change in 381 transcripts' expression in these mice compared to mCherry mice. Postmortem analysis showed hND6 mice had marked atrophy of the entire optic nerve, from the globe to the optic chiasm, and a significant loss of retinal ganglion cells compared to age-matched control mice (P = 1.7E-9).ConclusionsDelivered hND6T14484C induces visual loss and optic neuropathy in mice, the hallmarks of human Leber's hereditary optic neuropathy (LHON).Translational relevanceResults from this study will help establish a novel strategy not only to generate an LHON animal model but also to provide a potential to treat this or any other mitochondrial diseases.
| S-EPMC7545076 | biostudies-literature
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.
2020-03-09 | ST001327 | MetabolomicsWorkbench
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
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 | GSE207928 | GEO
Project description:EAE mice were injected with LPC 18:1 and Isobaric C13-His at the optic nerve when they exhibited a clinical score of 2. Visual function was assessed via pattern electroretinogram and optic nerves were harvested 12 days post optic nerve injection. Optic nerves were processed for mass spectrometry to identify the integration of C13-His in newly synthesized proteins.
2022-02-17 | PXD025176 | Pride
Project description:Optic nerves are an accessible part of the CNS, providing a source of glia without the presence of neuronal cell bodies. Therefore, an analysis was carried out of gene expression in optic nerves at P4, before myelination begins and at P10, when myelination is very actively proceeding. The goal was to obtain a profile of the changing gene expression that accompanies this transition from unmyelinated CNS nerve to myelinated nerve. Two microarray experiments were combined here. In the first, RNA was prepared from the optic nerves of 75 P4 C57BL/6J mice and 70 P10 C57BL/6J mice. In the second experiment, RNA was prepared from the optic nerves of 55 P4 C57BL/6J mice and two groups of 50 P10 C57Bl/6J mice. In total, there are 2 P4 RNA samples and 3 P10 RNA samples being hybridized to Affymetrix GeneChip 430A for Mouse Expression.
2011-05-16 | E-GEOD-24513 | biostudies-arrayexpress
Project description:In many human disorders mitochondrial dysfunction is central to degeneration of retinal ganglion cells. As these cells do not regenerate, vision is irreversibly lost. Here we show reversal of visual dysfunction by a mitochondrially targeted adeno associated virus in transgenic mice harboring a G11778A mutation in the ND4 subunit of complex I persists longterm and it is associated with reduced loss of RGCs and their axons, improved oxidative phosphorylation, persistence of transferred ND4 DNA and transcription of ND4 mRNA.
| S-EPMC5882860 | biostudies-other
Project description:EAE mice were injected with LPC 18:1 at the optic nerve when they exhibited a clinical score of 2. Visual function was assessed via pattern electroretinogram and optic nerves were harvested 12 days post optic nerve injection. Three different visual recovery pathways were observed: 1) No-injection control (no recovery in visual function), 2) Low recovery visual function, 3) High recovery visual function and 4) No change in visual function.
2022-02-17 | PXD024966 | Pride
Project description:Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy
| PRJNA857697 | ENA