Characterization of chromatin accessibility changes in retinal ganglion cells (RGCs) following optic nerve crush
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE184547 | GEO | 2022/05/06
REPOSITORIES: GEO
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Project description:Through a comparative analysis of RGC subclasses exhibiting varying levels of resilience to cell death, based on cell-cell interaction analysis, we identified the Mu-opioid receptor, encoded by the Oprm1 gene, as a novel neuroprotective factor for pan-RGCs. Functionally and with the sequencing dataset deposited here, we validated Oprm1 as a neuroprotective factor for RGCs, by demonstrating that overexpression of Oprm1 in RGCs not only led to a markedly increased survival rate of RGCs following several different types of retinal injuries, but also significantly improved visually-guided perception behaviors.
2023-12-26 | GSE248537 | GEO
Project description:Retinal ganglion cells (RGCs) convey the major output of information collected from the eye to the brain. RGCs are irreversibly lost when injured in degenerative diseases such as glaucoma; this failure can be partially reversed by eliminating the retinal mobile zinc (Zn2+) and leads to substantial axon regeneration. ZnT3 conditional knockout in retinal amacrine cells blocks the synaptic transport of Zn2+, which promotes RGC survival and axonal regeneration in optic nerve jinjury (ONC). Here, we conducted an mRNA sequencing of flow cytometry-isolated RGCs 3 days after optic nerve injury with or without ZnT3 expression in retinal amacrine cells.
2023-07-01 | GSE213937 | GEO
Project description:Characterization of chromatin accessibility changes in retinal ganglion cells (RGCs) following optic nerve crush
| PRJNA765016 | ENA
Project description:Glaucoma is a neurodegenerative disease with retinal ganglion cell (RGC) loss, optic nerve degeneration and subsequent vision loss. There are about 30 different subtypes of RGCs whose response to glaucomatous injury is not well characterized. The purpose of this study was to evaluate the response of 4 RGC subtypes in a mouse model of optic nerve crush (ONC). In this study, we also evaluated the pattern of axonal degeneration in RGC subtypes after nerve injury. We found that out of the 4 subtypes, transient-Off α RGCs are the most susceptible to injury followed by On-Off direction selective RGCs (DSGC). Non-image forming RGCs are more resilient with ipRGCs exhibiting the most resistance of them all. In contrast, axons degenerate irrespective of their retinal soma after ONC injury. In conclusion, we show that RGCs have subtype specific cell death response to ONC injury and that RGC axons disintegrate in an autonomous fashion undergoing Wallerian degeneration. These discoveries can further direct us towards effective diagnostic and therapeutic approaches to treat optic neuropathies, such as glaucoma.
| S-EPMC6054657 | biostudies-literature
Project description:Retinal ganglion cells (RGCs) convey the major output of information collected from the eye to the brain. RGCs are irreversibly lost when injured in degenerative diseases such as glaucoma; this failure can be partially reversed by eliminating the retinal mobile zinc (Zn2+) and leads to substantial axon regeneration. Here, we conducted an mRNA sequencing of flow cytometry-isolated RGCs 3 days after optic nerve injury (NC) with or without TPEN treatment. We identified differentially expressed genes using a cutoff of at least 1.5-fold change and FDR of at least 0.05. We focused on the intersecting genes that were upregulated after NC and recovered in TPEN (TPEN/NC; fold change < -1.5; P < 0.05), namely, TPEN target genes.
2022-11-02 | GSE208777 | GEO
Project description:To gain a deeper insight into roles of Arid1a in injured retinal ganglion cells (RGCs), we performed ATAC-seq and RNA-seq to analyze the genome-wide changes of chromatin accessibility and transcriptome changes before and after Arid1a deletion in RGCs of the adult mouse using Cre-lox system.
2020-04-20 | GSE147844 | GEO
Project description:To study sequential changes in retinal ganglion cell (RGC) morphology in mice after optic nerve crush and after induction of experimental glaucoma.Nerve crush or experimental glaucoma was induced in mice that selectively express yellow fluorescent protein (YFP) in RGCs. Mice were euthanized 1, 4, and 9 days after crush and 1, 3, and 6 weeks after induction of glaucoma by bead injection. All YFP-RGCs were identified in retinal whole mounts. Then confocal images of randomly selected RGCs were quantified for somal fluorescence brightness, soma size, neurite outgrowth, and dendritic complexity (Sholl analysis).By 9 days after crush, 98% of RGC axons died and YFP-RGCs decreased by 64%. After 6 weeks of glaucoma, 31% of axons died, but there was no loss of YFP-RGC bodies. All crush retinas combined had significant decreases in neurite outgrowth parameters (P ? 0.036, generalized estimating equation [GEE] model) and dendritic complexity was lower than controls (P = 0.017, GEE model). There was no change in RGC soma area after crush. In combined glaucoma data, the RGC soma area was larger than control (P = 0.04, GEE model). At 3 weeks, glaucoma RGCs had significantly larger values for dendritic structure and complexity than controls (P = 0.044, GEE model), but no statistical difference was found at 6 weeks.After nerve crush, RGCs and axons died rapidly, and dendritic structure decreased moderately in remaining RGCs. Glaucoma caused an increase in RGC dendrite structure and soma size at 3 weeks.
| S-EPMC3630905 | biostudies-other
Project description:Objective: To identify genes that are differentially expressed in retinal ganglion cells undergoing axon regeneration after optic nerve injury. Adult mice that express cyan-fluorescent protein (CFP) in RGCs were treated with pro-regenerative treatment after optic nerve injury. The treated RGCs were selected by FACS (CFP+mcherry) and their RNA profiles were analyzed.
2020-12-29 | GSE142881 | GEO
Project description:The purpose of this study was to characterize the miRNA profile of purified retinal ganglion cells (RGC) from healthy and diseased rat retina. Diseased retina includes those after a traumatic optic nerve crush (ONC), and after ocular hypertension/glaucoma. Rats were separated into four groups: healthy/intact, 7 days after laser-induced ocular hypertension, 2 days after traumatic ONC, and 7 days after ONC. RGC were purified from rat retina using microbeads conjugated to CD90.1/Thy1. RNA were sequenced using Next Generation Sequencing. Over 100 miRNA were identified that were significantly different in diseased retina compared to healthy retina. Considerable differences were seen in the miRNA expression of RGC 7 days after ONC, whereas after 2 days, few changes were seen. The miRNA profiles of RGC 7 days after ONC and 7 days after ocular hypertension were similar, but discrete miRNA differences were still seen. Candidate mRNA showing different levels of expression after retinal injury were manipulated in RGC cultures using mimics/AntagomiRs. Of the five candidate miRNA identified and subsequently tested for therapeutic efficacy, miR-194 inhibitor and miR-664-2 inhibitor elicited significant RGC neuroprotection, whereas miR-181a mimic and miR-181d-5p mimic elicited significant RGC neuritogenesis.
| S-EPMC8305746 | biostudies-literature
Project description:PurposeOptic nerve (ON) injuries can result in vision loss via structural damage and cellular injury responses. Understanding the immune response, particularly the role of macrophages, in the cellular response to ON injury is crucial for developing therapeutic approaches which affect ON injury repair. The present study investigates the role of macrophages in ON injury response, fibrotic scar formation, and retinal ganglion cell (RGC) function.MethodsThe study utilizes macrophage Fas-induced apoptosis (MaFIA) mice to selectively deplete hematogenous macrophages and explores the impact macrophages have on ON injury responses. Histological and immunofluorescence analyses were used to evaluate macrophage expression levels and fibrotic scar formation. Pattern electroretinogram (PERG) recordings were used to assess RGC function as result of ON injury.ResultsSuccessful macrophage depletion was induced in MaFIA mice, which led to reduced fibrotic scar formation in the ON post-injury. Despite an increase in activated macrophages in the retina, RGC function was preserved, as demonstrated by normal PERG waveforms for up to 2 months post-injury. The study suggests a neuroprotective role for macrophage depletion in ON damage repair and highlights the complex immune response to ON injury.ConclusionsTo our knowledge, this study is the first to use MaFIA mice to demonstrate that targeted depletion of hematogenous macrophages leads to a significant reduction in scar size and the preservation of RGC functionality after ON injury. These findings highlight the key role of hematogenous macrophages in the response to ON injury and opens new avenues for therapeutic interventions in ON injuries. Future research should focus on investigating the distinct roles of macrophage subtypes in ON injury and potential macrophage-associated molecular targets to improve ON regeneration and repair.
| S-EPMC11328886 | biostudies-literature