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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE247314 | GEO | 2023/11/08

REPOSITORIES: GEO

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Knocking Out Non-muscle Myosin II in Retinal Ganglion Cells Promotes Long-Distance Optic Nerve Regeneration.

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 show that knocking out myosin IIA and IIB (myosin IIA/B) in retinal ganglion cells alone, either before or after optic nerve crush, induces significant optic nerve regeneration. Combined Lin28a overexpression and myosin IIA/B knockout lead to an additive promoting effect and long-distance axon regeneration. Immunostaining, RNA sequencing, and western blot analyses reveal that myosin II deletion does not affect known axon regeneration signaling pathways or the expression of regeneration-associated genes. Instead, it abolishes the retraction bulb formation and significantly enhances the axon extension efficiency. The study provides clear evidence that directly targeting neuronal cytoskeleton is sufficient to induce significant CNS axon regeneration and that combining altered gene expression in the soma and modified cytoskeletal dynamics in the axon is a promising approach for long-distance CNS axon regeneration.

| S-EPMC7219759 | biostudies-literature

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)

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

2020-03-22 | GSE147328 | GEO

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

Project description:Knocking out non-muscle myosin II in retinal ganglion cells promotes long-distance optic nerve regeneration

| PRJNA1037094 | ENA

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

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

| PRJNA614479 | ENA

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

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

| PRJNA613823 | ENA

Translational profiling of retinal ganglion cell optic nerve regeneration in Xenopus laevis.

Project description:Unlike adult mammals, adult frogs regrow their optic nerve following a crush injury, making Xenopus laevis a compelling model for studying the molecular mechanisms that underlie neuronal regeneration. Using Translational Ribosome Affinity Purification (TRAP), a method to isolate ribosome-associated mRNAs from a target cell population, we have generated a transcriptional profile by RNA-Seq for retinal ganglion cells (RGC) during the period of recovery following an optic nerve injury. Based on bioinformatic analysis using the Xenopus laevis 9.1 genome assembly, our results reveal a profound shift in the composition of ribosome-associated mRNAs during the early stages of RGC regeneration. As factors involved in cell signaling are rapidly down-regulated, those involved in protein biosynthesis are up-regulated alongside key initiators of axon development. Using the new genome assembly, we were also able to analyze gene expression profiles of homeologous gene pairs arising from a whole-genome duplication in the Xenopus lineage. Here we see evidence of divergence in regulatory control among a significant proportion of pairs. Our data should provide a valuable resource for identifying genes involved in the regeneration process to target for future functional studies, in both naturally regenerative and non-regenerative vertebrates.

| S-EPMC5897040 | biostudies-literature

Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury.

Project description:Spermidine acts as an endogenous free radical scavenger and inhibits the action of reactive oxygen species. In this study, we examined the effects of spermidine on retinal ganglion cell (RGC) death in a mouse model of optic nerve injury (ONI). Daily ingestion of spermidine reduced RGC death following ONI and sequential in vivo retinal imaging revealed that spermidine effectively prevented retinal degeneration. Apoptosis signal-regulating kinase-1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase kinase kinase and has an important role in ONI-induced RGC apoptosis. We demonstrated that spermidine suppresses ONI-induced activation of the ASK1-p38 mitogen-activated protein kinase pathway. Moreover, production of chemokines important for microglia recruitment was decreased with spermidine treatment and, consequently, accumulation of retinal microglia is reduced. In addition, the ONI-induced expression of inducible nitric oxide synthase in the retina was inhibited with spermidine treatment, particularly in microglia. Furthermore, daily spermidine intake enhanced optic nerve regeneration in vivo. Our findings indicate that spermidine stimulates neuroprotection as well as neuroregeneration, and may be useful for treatment of various neurodegenerative diseases including glaucoma.

| S-EPMC4650557 | biostudies-other

The Retinal Ganglion Cell Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration Consortium

Project description: Not available

| S-EPMC10630665 | biostudies-literature

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

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