Epigenetic Regulation of Optic Nerve Development, Protection, and Repair

Ashok, Ajay; Pooranawattanakul, Sarita; Tai, Wai Lydia; Cho, Kin‐Sang; Utheim, Tor Paaske; Cestari, Dean M.; Chen, Dong F.

doi:10.3390/ijms23168927

Cited by 7 publications

(7 citation statements)

References 96 publications

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“…Our study suggests that ES alters epigenetic modification namely, DNA demethylation or TET expression. DNA demethylation in retina is vital for development, 3,4 and TET knockout mice exhbiit oligodendrocyte differentiation defects and a reduced capability for axon remyelination following injury 4,5 . In ocular injury models of adult mice, DNA methylation reportedly upregulated, resulting in constricted DNA‐histone configuration that limits vital gene translation 4 .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the field of epigenetics has received much attention in the wake of discoveries of epigenetic factors that influence disease progression and the functions of cellular regenerative machinery 3‐5 . Epigenetics modifications, such as DNA and histone methylation and demethylation, play a vital role in RGC homeostasis, regeneration, and protection 3,6 . Most of the factors and enzymes that fuel these epigenetic events have only been emerging in the past few decades.…”

Section: Introductionmentioning

confidence: 99%

“…cellular regenerative machinery. [3][4][5] Epigenetics modifications, such as DNA and histone methylation and demethylation, play a vital role in RGC homeostasis, regeneration, and protection. 3,6 Most of the factors and enzymes that fuel these epigenetic events have only been emerging in the past few decades.…”

mentioning

confidence: 99%

“…[3][4][5] Epigenetics modifications, such as DNA and histone methylation and demethylation, play a vital role in RGC homeostasis, regeneration, and protection. 3,6 Most of the factors and enzymes that fuel these epigenetic events have only been emerging in the past few decades. Among these factors, ten-eleven translocation (TET) protein family are mainly responsible for DNA demethylation and several studies report that their expression is important for ocular tissue homeostasis and regeneration.…”

mentioning

confidence: 99%

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Electrical stimulation alters DNA methylation and promotes neurite outgrowth

Ashok,

Tai,

Lennikov

et al. 2023

J of Cellular Biochemistry

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Electrical stimulation (ES) influences neural regeneration and functionality. We here investigate whether ES regulates DNA demethylation, a critical epigenetic event known to influence nerve regeneration. Retinal ganglion cells (RGCs) have long served as a standard model for central nervous system neurons, whose growth and disease development are reportedly affected by DNA methylation. The current study focuses on the ability of ES to rescue RGCs and preserve vision by modulating DNA demethylation. To evaluate DNA demethylation pattern during development, RGCs from mice at different stages of development, were analyzed using qPCR for ten‐eleven translocation (TETs) and immunostained for 5 hydroxymethylcytosine (5hmc) and 5 methylcytosine (5mc). To understand the effect of ES on neurite outgrowth and DNA demethylation, cells were subjected to ES at 75 µAmp biphasic ramp for 20 min and cultured for 5 days. ES increased TETs mediated neurite outgrowth, DNA demethylation, TET1 and growth associated protein 43 levels significantly. Immunostaining of PC12 cells following ES for histone 3 lysine 9 trimethylation showed cells attained an antiheterochromatin configuration. Cultured mouse and human retinal explants stained with β‐III tubulin exhibited increased neurite growth following ES. Finally, mice subjected to optic nerve crush injury followed by ES exhibited improved RGCs function and phenotype as validated using electroretinogram and immunohistochemistry. Our results point to a possible therapeutic regulation of DNA demethylation by ES in neurons.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Electrical stimulation alters DNA methylation and promotes neurite outgrowth

Ashok,

Tai,

Lennikov

et al. 2023

J of Cellular Biochemistry

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“…Epigenetic factors are known to influence tissue development, functionality, and their response to pathophysiology. In their review, Ashok et al [ 3 ] focus on different types of epigenetic regulators and their associated molecular apparatus that affect the optic nerve. They emphasize that a comprehensive understanding of epigenetic regulation in optic nerve development and homeostasis should help unravel novel molecular pathways and pave the way to design blueprints for effective therapeutics to address optic nerve protection, repair, and regeneration.…”

Section: Reviewsmentioning

confidence: 99%

Optic Neuropathies: Current and Future Strategies for Optic Nerve Protection and Repair

Miller

Tsai

2023

IJMS

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The Lysine Demethylase KDM7A Regulates Immediate Early Genes in Neurons

et al. 2023

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Lysine demethylase KDM7A removes histone modifications H3K9me1/2 and H3K27me1/2. KDM7A plays critical roles in gene expression and contribute to biological processes including tumorigenesis, metabolism, and embryonic development. However, the functions of KDM7A in mammalian nervous system are still poorly explored. In this study, functional roles of KDM7A are comprehensively investigated in neuronal cells by applying CUT&Tag‐seq, RNA‐seq and mice models. Knockdown of Kdm7a in N2A cells result in the alteration of histone modifications near transcription start sites (TSSs) and the expression changes of a large number of genes. In particular, the expression of immediate early genes (IEGs), a series of genes maintaining the function of the nervous system and associating with neurological disorders, are significantly decreased upon Kdm7a knockdown. Furthermore, in vivo knockdown of Kdm7a in dentate gyrus (DG) neuron of mice hippocampus, via Adeno‐associated virus (AAV)‐based stereotaxic microinjection, led to a significant decrease of the expression of c‐Fos, a marker of neuron activity. Behavior assays in mice further revealed that Kdm7a knockdown in hippocampus repress neuron activity, which leading to impairment of emotion and memory. Collectively, the study reveals that KDM7A affects neuron functions by regulating IEGs, which may provide new clues for understanding epigenetic mechanisms in neurological disorders.

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Epigenetic Regulation of Optic Nerve Development, Protection, and Repair

Cited by 7 publications

References 96 publications

Electrical stimulation alters DNA methylation and promotes neurite outgrowth

Electrical stimulation alters DNA methylation and promotes neurite outgrowth

Optic Neuropathies: Current and Future Strategies for Optic Nerve Protection and Repair

The Lysine Demethylase KDM7A Regulates Immediate Early Genes in Neurons

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