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Whole genome bisulfite-seq analysis of control and Dnmt3a conditional knockout (cKO) retinal ganglion cells at 2 days post optic nerve crush

ABSTRACT: Dnmt3a deficiency in retinal ganglion cells promotes axon regeneration in an optic nerve crush mouse model. To investigate the contribution of Dnmt3a to DNA methylation and axon regeneration, retinal ganglion cells isolated from control and retinal ganglion cell-specific Dnmt3a knockout mice at 2 days post-crush were applied for whole genome bisulfite-seq analysis by Illumina NovaSeq 6000.

ORGANISM(S): Mus musculus

PROVIDER: GSE229034 | GEO | 2023/12/14

REPOSITORIES: GEO

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Bulk RNA-seq analysis of control and Dnmt3a conditional knockout (cKO) retinal ganglion cells at 2 days post optic nerve crush

Project description:Dnmt3a deficiency in retinal ganglion cells promotes axon regeneration in an optic nerve crush mouse model. To investigate the role of Dnmt3a in axon regeneration, retinal ganglion cells isolated from control and retinal ganglion cell-specific Dnmt3a knockout mice at 2 days post-crush were applied for Bulk RNA-seq analysis by NovaSeq platform.

2023-12-14 | GSE229033 | GEO

Single nuclei RNA-seq analysis of control and Dnmt3a conditional knockout (cKO) of retinal ganglion cells at 2 days post optic nerve crush.

Project description:Dnmt3a deficiency in retinal ganglion cells promotes axon regeneration in an optic nerve crush mouse model. To investigate the role of Dnmt3a in axon regeneration, retinal ganglion cell nuclei were sorted from control and retinal ganglion cell-specific Dnmt3a knockout mice at 2 days post optic nerve crush and applied for single nuclei RNA-seq analysis by 10X Genomics technology.

2023-12-14 | GSE228627 | GEO

Aldose reductase inhibition decelerates optic nerve degeneration by suppressing retinal microglia activation

Project description:To investigate the role of aldose reductase (AR) inhibition using Sorbinil on retinal microglia (RMG) activation, retinal ganglion cell (RGC) survival, and axon regeneration after optic nerve trauma. We observed that AR inhibition using Sorbinil attenuates RMG activation and subsequently promotes RGC survival and delays axon degeneration one week after optic nerve crush.

2023-04-05 | GSE200233 | GEO

Differential response of C57BL/6J mouse and DBA/2J mouse to optic nerve crush

Project description:Retinal ganglion cell (RGC) death is the final consequence of many blinding diseases, where there is considerable variation in the time course and severity of RGC loss. Indeed, this process appears to be influenced by a wide variety of genetic and environmental factors. In this study we explored the genetic basis for differences in ganglion cell death in two inbred strains of mice. We found that RGCs are more susceptible to death following optic nerve crush in C57BL/6J mice (54% survival) than in DBA2/J mice (62% survival). Using the Illumina Mouse-6 microarray, we identified 1,580 genes with significant change in expression following optic nerve crush in these two strains of mice. Our analysis of the changes occurring after optic nerve crush demonstrated that the greatest amount of change (44% of the variance) was due to the injury itself. This included changes associated with ganglion cell death, reactive gliosis, and abortive regeneration. The second pattern of gene changes (23% of the variance) was primarily related to differences in gene expressions observed between the C57BL/6J and DBA/2J mouse strains. The remaining changes in gene expression represent interactions between the effects of optic nerve crush and the genetic background of the mouse. We extracted one genetic network from this dataset that appears to be related to tissue remodeling. One of the most intriguing sets of changes included members of the crystallin family of genes, which may represent a signature of pathways modulating the susceptibility of cells to death. Differential responses to optic nerve crush between two widely used strains of mice were used to define molecular networks associated with ganglion cell death and reactive gliosis. These results form the basis for our continuing interest in the modifiers of retinal injury. 18 Samples: 9 per strain (C57BL/6J & DBA/2J); 3 conditions per strain

2010-08-19 | E-GEOD-17117 | biostudies-arrayexpress

Knocking out non-muscle myosin II in retinal ganglion cells promotes long-distance optic nerve regeneration (RNA-Seq II)

Project description:In addition to altered gene expression, pathological cytoskeletal dynamics in the axon are another key intrinsic barrier for axon regeneration in the central nervous system (CNS). Here we showed that knocking out myosin IIA/B in retinal ganglion cells alone either before or after optic nerve crush induced significant optic nerve regeneration. Combined Lin28a overexpression and myosin IIA/B knockout led to additive promoting effect and long-distance axon regeneration. Immunostaining, RNA sequencing and western blot analyses revealed that myosin II deletion did not affect known axon regeneration signaling pathways or the expression of regeneration associated genes. Instead, it abolished the retraction bulb formation and significantly enhanced the axon extension efficiency. The study provided clear evidence that directly targeting neuronal cytoskeleton was sufficient to induce significant CNS axon regeneration, and combining altered gene expression in the soma and modified cytoskeletal dynamics in the axon was a promising approach for long-distance CNS axon regeneration

2020-03-24 | GSE147400 | GEO

Knocking out non-muscle myosin II in retinal ganglion cells promotes long-distance optic nerve regeneration (RNA-Seq I)

2020-03-22 | GSE147328 | GEO

Gene expression timecourse in zebrafish whole eye in response to optic nerve crush

Project description:It is well-established that neurons in the adult mammalian central nervous system are terminally differentiated and, if injured, will be unable to regenerate their connections. In contrast to mammals, zebrafish and other teleosts display a robust neuroregenerative response. Following optic nerve crush (ONX), retinal ganglion cells (RGC) regrow their axons to synapse with topographically correct targets in the optic tectum, such that vision is restored in ~21 days. What accounts for these differences between teleostean and mammalian responses to neural injury is not fully understood. A time course analysis of global gene expression patterns in the zebrafish eye after optic nerve crush can help to elucidate cellular and molecular mechanisms that contribute to a successful neuroregeneration. We used microarrays to detail the global gene expression patterns underlying a successful regeneration or the optic nerve following injury. Experiment Overall Design: Microarray analysis was performed on total RNA extracted from whole eye following optic nerve crush (ONX) or sham surgery at defined intervals (4, 12, & 21 days).

2010-02-21 | E-GEOD-19298 | biostudies-arrayexpress

Differential response of C57BL/6J mouse and DBA/2J mouse to optic nerve crush

2009-07-16 | GSE17117 | GEO

Transcriptional profiling of adult retinal ganglion cells during optic nerve regeneration

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

Single-cell profiles of retinal neurons differing in resilience to injury reveal neuroprotective genes - Time course of transcriptomic changes in single retinal ganglion cells following optic nerve crush

Project description:Neuronal types in the central nervous system differ dramatically in their resilience to injury or insults. Here we studied selective resilience in mouse retinal ganglion cells (RGCs) following optic nerve crush (ONC), which severs their axons and leads to death of ~80% of RGCs in 2 weeks. To identify expression programs associated with differential resilience, we first used single-cell RNA-seq (scRNA-seq) to generate a comprehensive molecular atlas of 45 RGC types in adult retina. We tracked their survival after ONC, characterized transcriptomic, morphological, and physiological changes that preceded degeneration, and identified genes selectively expressed by each type. Finally, loss- and gain-of-function assays in vivo showed that manipulating some of these genes improved neuronal survival and axon regeneration following ONC. This study provides a systematic framework for parsing type-specific responses to injury, and demonstrates that these responses can be used to reveal molecular targets for intervention.

2019-11-27 | GSE137398 | GEO

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