Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Astrocytes of the optic nerve exhibit a region-specific and temporally distinct response to elevated intraocular pressure

ABSTRACT: The optic nerve is an important tissue in glaucoma and the unmyelinated nerve head region remains an important site of many early neurodegenerative changes. In humans and mice, astrocytes constitute the major glial cell type in the region, and in glaucoma they become reactive, influencing the optic nerve head (ONH) microenvironment and disease outcome. To determine the response of ONH astrocytes in glaucoma, we studied their transcriptional response to an elevation in intraocular pressure (IOP) induced by the microbead occlusion model. We also assessed the response of astrocytes in the more distal myelinated optic nerve proper (ONP). In this experimental model, astrocytes of the optic nerve exhibited a region-specific and temporally distinct response: ONH astrocytes showed very few early transcriptional changes and ONP astrocytes demonstrated substantially larger changes over the course of the experiment.

ORGANISM(S): Mus musculus

PROVIDER: GSE237073 | GEO | 2023/10/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma

Project description:A major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated region is differentially susceptible to IOP-induced damage in rodent models and in human glaucoma. While several studies have analyzed gene expression changes in the mouse optic nerve following optic nerve injury, few were designed to consider the regional gene expression differences that exist between these distinct areas. We performed bulk RNA-sequencing on the retina and on separately micro-dissected unmyelinated and myelinated optic nerve regions from naïve C57BL/6 mice, mice after optic nerve crush, and mice with microbead-induced experimental glaucoma (total = 36). Gene expression patterns in the naïve unmyelinated optic nerve showed significant enrichment of the Wnt, Hippo, PI3K-Akt, and transforming growth factor β pathways, as well as extracellular matrix–receptor and cell membrane signaling pathways, compared to the myelinated optic nerve and retina. Gene expression changes induced by both injuries were more extensive in the myelinated optic nerve than the unmyelinated region, and greater after nerve crush than glaucoma. Changes present three and fourteen days after injury largely subsided by six weeks. Gene markers of reactive astrocytes did not consistently differ between injury states. Overall, the transcriptomic phenotype of the mouse unmyelinated optic nerve was significantly different from immediately adjacent tissues, likely dominated by expression in astrocytes, whose junctional complexes are inherently important in responding to IOP elevation.

2023-09-06 | GSE241782 | GEO

Transcriptomic analyses of astrocyte heterogeneity within white matter tracts

Project description:Astrocytes are broadly categorized as protoplasmic or fibrous, with the former localized to synaptically dense gray matter regions and the latter associated with axons in the white matter. Much of what we know about astrocyte form and function is derived from the study of protoplasmic astrocytes, whereas fibrous astrocytes remain relatively unexplored. We investigated the transcriptome of uninjured fibrous astrocytes in the mouse from three regions: unmyelinated optic nerve head (ONH), myelinated optic nerve proper (ONP), and corpus callosum (CC).

2022-11-29 | GSE211515 | GEO

Sub-region-Specific Optic Nerve Head Glial Activation in Glaucoma

Project description:Glaucoma, a multifactorial neurodegenerative disease characterized by progressive loss of retinal ganglion cells and their axons in the optic nerve, is a leading cause of irreversible vision loss. Intraocular pressure (IOP) is a risk factor for axonal damage, which initially occurs at the optic nerve head (ONH). Complex cellular and molecular mechanisms involved in the pathogenesis of glaucomatous optic neuropathy remain unclear. Here we define early molecular events in the ONH in an inherited large animal glaucoma model in which ONH structure resembles that of humans. Gene expression profiling of ONH tissues from rigorously phenotyped feline subjects with early-stage glaucoma and precisely age-matched controls was performed by RNA-sequencing (RNA-seq) analysis and complementary bioinformatic approaches applied to identify molecular processes and pathways of interest. Immunolabeling supported RNA-seq findings while providing cell-, region-, and disease stage–specific context in the ONH in situ. Transcriptomic evidence for cell proliferation and immune/inflammatory responses is identifiable in early glaucoma, soon after IOP elevation and prior to morphologically detectable axon loss, in this large animal model. In particular, proliferation of microglia and oligodendrocyte precursor cells is a prominent feature of early-stage, but not chronic, glaucoma. ONH microgliosis is a consistent hallmark in both early and chronic stages of glaucoma. Molecular pathways and cell type–specific responses strongly implicate toll-like receptor and NF-κB signaling in early glaucoma pathophysiology. The current study provides critical insights into molecular pathways, highly dependent on cell type and sub-region in the ONH even prior to irreversible axon degeneration in glaucoma.

2020-04-07 | GSE110019 | GEO

Transcription profiling of human optic nerve astrocytes from Caucasian and African Americans with or without glaucoma

Project description:This SuperSeries is composed of the following subset Series:; GSE9939: Gene expression data on human optic nerve head astrocytes in normal Caucasian and African americans; GSE9944: Gene expression data on human optic nerve head astrocytes in Caucasian and African americans with or without glaucoma Experiment Overall Design: Refer to individual Series

2008-04-07 | E-GEOD-9963 | biostudies-arrayexpress

Transcription profiling of human optic nerve head astrocytes from normal and glaucoma patients

Project description:Astrocytes from optic nerve head from donors with and without glaucoma

2007-08-21 | E-GEOD-2378 | biostudies-arrayexpress

Expression data from mouse optic nerve head after elevation in intraocular pressure

Project description:Reactive astrocytes are typically studied in models that cause irreversible mechanical damage to axons, neuronal cell bodies, and glia. We evaluated the response of astrocytes in the optic nerve head to a subtle injury induced by a brief, mild elevation of the intraocular pressure. Astrocytes demonstrated reactive remodeling showing hypertrophy, process retraction and simplification of their shape. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of astrogliosis in response to this subtle injury. Six- to eight-week old C57Bl/6 male mice were used in this experiment. One eye underwent an elevation in intraocular pressure to 30 mmHg for 1 hour and then allowed to recover for 3 days. The contralateral eye served as a control. Due to the small tissue size of the mouse optic nerve head, two optic nerve heads were pooled together for each microarray chip. We used 10 mice to generate five biological replicates for each condition.

2013-05-17 | E-GEOD-40009 | biostudies-arrayexpress

Normal and glaucomatous astrocytes

Project description:Astrocytes from optic nerve head from donors with and without glaucoma Keywords: parallel sample

2005-03-09 | GSE2378 | GEO

Transcription profiling of human optic nerve head astrocytes in Caucasian and African americans with or without glaucoma

Project description:To determine whether optic nerve head astrocytes, a key cellular component of glaucomatous neuropathy, exhibit differential gene expression in primary culture of astrocytes from African American donors with or without glaucoma, compared to astrocytes from Caucasian American donors with or without glaucoma. Experiment Overall Design: We divided samples into four group: Caucasian American normal, Caucasian American with glaucoma, African American normal and African American with glaucoma. We analyzed data from Affymetrix Human Genome U133A 2.0 and U95 chips.

2008-04-07 | E-GEOD-9944 | biostudies-arrayexpress

Gene expression data on human optic nerve head astrocytes in Caucasian and African americans with or without glaucoma

2008-01-31 | GSE9944 | GEO