Time-Resolved Single-Nucleus Transcriptomic Mapping of Neuro–Glial–Vascular Communication in the Hyperacute-to-Acute Stages of Optic Nerve Injury
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE304709 | GEO | 2026/06/30
REPOSITORIES: GEO
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Project description:Time-Resolved Single-Nucleus Transcriptomic Mapping of Neuro–Glial–Vascular Communication in the Hyperacute-to-Acute Stages of Optic Nerve Injury
| PRJNA1302379 | ENA
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
Project description:Reactive gliosis is a complex process that involves profound changes in gene expression. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of reactive gliosis in optic nerve head in response to optic nerve crush injury. C57Bl/6 female mice were 6-8 weeks old at the time of optic nerve crush surgery. The optic nerve in the left eye was crush 1 mm behind the globe for 10 seconds and the right eye served as contralateral control. The animals were allowed to recover for 1 day, 3 day, 1 week, 3 weeks and 3 months before the optic nerve heads were collected. The naive control mice did not receive any surgery in either eye. Due to the small tissue size of the mouse optic nerve head, two optic nerve heads were pooled together for each microarray chip. The left eyes and the right eyes of two mice were combined respectively to form one pair of experiment and control samples. There were five biological replicates (10 mice) for each condition.
2013-07-15 | E-GEOD-40857 | biostudies-arrayexpress
Project description:The optic nerve develops from the neuroectodermal optic stalk, which undergoes coordinated morphogenesis and gives rise to optic nerve astrocytes that support retinal ganglion cell (RGC) axons. Here, we define the progression of astrocyte formation from the optic stalk and identify stage‑specific functions of the SWI/SNF scaffolding subunits Smarcc1 (Baf155) and Smarcc2 (Baf170). Both factors are co‑expressed in retinal pigment epithelium (RPE) and optic stalk progenitors, with Smarcc2 persisting in differentiated RPE and astrocytes. Conditional deletion using Dct‑Cre revealed compensatory activity in pigmented lineages, whereas Smarcc1 loss uniquely disrupted optic nerve head (ONH) morphogenesis, resulting in glial lamina collapse, RGC degeneration, and progressive visual decline. Spatial transcriptomics and functional assays show that Smarcc1 enables dorsal optic stalk progenitors to transition from a pigmented, RPE‑like state to astrocyte progenitors by repressing pigment gene programs and permitting Pax2/Sox2 activity. After specification, Smarcc1 is also required for glial lamina assembly and astrocyte migration into the inner retina. These findings demonstrate that Smarcc1‑dependent chromatin remodeling coordinates astrocyte specification with ONH morphogenesis to maintain long‑term retinal function.
2026-06-29 | GSE336951 | GEO
Project description:Expression data from mouse optic nerve and optic tract
| PRJNA486823 | ENA
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
Project description:In order to identify the miRNAs in adult Dicer1-CKO Müller glia of the neural retina, we isolated the Müller glia from Rlbp-CreER: Stopf/f-tdTomato/Dicerf/f mice by means of fluorescent activated cell sorting and analyzed their miRNAs using NanoStrings Technologies®. miRNA expression of Dicer1-CKO Müller glia was compared to wild type Müller glia (a re-analyzed sample from GSE94759). We found that all highly expressed miRNAs declined in the Dicer-CKO leading to a disruption in retinal architecture over time.
2017-10-31 | GSE103098 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is an incurable disease characterized by proteinaceous aggregate accumulation and neuroinflammation culminating in rapidly progressive lower and upper motor neuron death. To interrogate cell-intrinsic and inter-cell type perturbations in ALS, single-nucleus RNA sequencing was performed on the lumbar spinal cord in the murine ALS model SOD1G93A transgenic and littermate control mice at peri-symptomatic onset stage of disease, age 90 days. This work uncovered perturbed tripartite synapse functions, complement activation and metabolic stress in the affected spinal cord; processes evidenced by cell death and proteolytic stress-associated gene sets. Concomitantly, these pro-damage events in the spinal cord co-existed with dysregulated reparative mechanisms. This work provides a resource of cell-specific niches in the ALS spinal cord and asserts that interwoven dysfunctional neuronal-glial communications mediating neurodegeneration are underway prior to overt disease manifestation and are recapitulated, in part, in the human post-mortem ALS spinal cord.
2022-02-18 | GSE173524 | GEO
Project description:Purpose. Immune privilege in the eye is a compilation of anti-inflammatory mechanisms that protect vision from the damaging sequelae of intense immune responses. Although the breakdown of privilege can lead to ocular disease, little is known about how these mechanisms are regulated. Since retinal Müller glial cells and autophagy also have anti-inflammatory properties, we tested the idea that Müller cells utilize autophagy to support immune privilege. Methods. The essential autophagy regulator Atg5 was deleted in retinal Muller cells using a tamoxifen inducible GlastCre ERT X Atg5f/f strain. Intraocular inflammation was induced by intravitreal injection of LPS and monitored by H&E staining, immunofluorescent confocal microscopy, and flow cytometry. scRNA-seq was performed on retinal Müller cells isolated from control and Atg5-deficient mice. Additionally, markers of Müller cell gliosis and function were assessed by western blotting and cytokines were detected by Luminex cytokine/chemokine arrays. In cultured Müller cells siRNA knockdown techniques were used to examine the role of autophagy in regulation of LPS-induced inflammatory pathways. Results. We observed increased and prolonged intraocular inflammation when Müller cells were autophagy (Atg5) deficient. Müller cell gliosis (as measured by Gfap expression) was significantly increased and inflammation was sustained over 5 days post-LPS injection compared to control. The retinae with Atg5-deficient Müller cells also contained increased inflammatory mediators and neuroprotective molecules. Gene expression analysis revealed a heterogeneous response to LPS in Müller glial cell population that revealed 2 states of activation. The normal retinae contain Müller cells in both a basal and an activated state, while autophagy deficient retinae (Atg5iΔMüller) contained only activated Müller cells. Analysis of gliosis markers Gfap and Lcn2 confirmed this heterogeneity showing that in control eyes basal and activated (gliotic) Müller glia were observed; however, with autophagy deficiency nearly all Müller cells were gliotic. Interestingly, activated cells were largely indistinguishable between autophagy sufficient and deficient Müller cells. In cultured Müller cells, siRNA knockdown of autophagy genes resulted in heightened mTOR activation, increased Gfap expression, and upregulated cytokine/chemokine production. Conclusions. Autophagy deficiency in Müller cells leads to enhanced intraocular inflammation though activation of the mTOR pathway. Our data suggests that autophagy defines a novel perspective on Müller glial heterogeneity based on their activation state. Thus, autophagy restrains cellular activation and inflammation, supporting immune privilege by preventing excessive and potentially destructive immune responses.
2025-09-10 | GSE293132 | GEO
Project description:Reactive gliosis is a complex process that involves profound changes in gene expression. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of reactive gliosis in optic nerve head in response to optic nerve crush injury.
2013-07-15 | GSE40857 | GEO