Optic nerve crush induces spatial and temporal gene expression patterns in retina and optic nerve of BALB/cJ mice

It is well-established that neurons in the adult mammalian central nervous system (CNS) 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 ONX can help to elucidate cellular and molecular mechanisms that contribute to a successful neuroregeneration. To define different phases of regeneration after ONX, alpha tubulin 1 ( tuba1) and growth-associated protein 43 ( gap43), markers previously shown to correspond to morphophological events, were measured by real time quantitative PCR (qPCR). Microarray analysis was then performed at defined intervals (6 hours, 1, 4, 12, and 21 days) post-ONX and compared to SHAM. Results show that optic nerve damage induces multiple, phase-related transcriptional programs, with the maximum number of genes changed and highest fold-change occurring at 4 days. Several functional groups affected by optic nerve regeneration, including cell adhesion, apoptosis, cell cycle, energy metabolism, ion channel activity, and calcium signaling, were identified. Utilizing the whole eye allowed us to identify signaling contributions from the vitreous, immune and glial cells as well as the neural cells of the retina. Comparisons between our dataset and transcriptional profiles from other models of regeneration in zebrafish retina, heart and fin revealed a subset of commonly regulated transcripts, indicating shared mechanisms in different regenerating tissues. Knowledge of gene expression patterns in all components of the eye in a model of successful regeneration provides an entry point for functional analyses, and will help in devising hypotheses for testing normal and toxic regulatory factors.

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Early Gene Expression Profile in Retinal Ganglion Cell Layer After Optic Nerve Crush in Mice

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.17-22438 ◽

2018 ◽

Vol 59 (1) ◽

pp. 370 ◽

Cited By ~ 3

Author(s):

Satoru Ueno ◽

Azusa Yoneshige ◽

Yoshiki Koriyama ◽

Man Hagiyama ◽

Yoshikazu Shimomura ◽

...

Keyword(s):

Gene Expression ◽

Optic Nerve ◽

Ganglion Cell ◽

Ganglion Cell Layer ◽

Cell Layer ◽

Early Gene ◽

Optic Nerve Crush ◽

Retinal Ganglion ◽

Nerve Crush ◽

Retinal Ganglion Cell Layer

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Comprehensive regional and temporal gene expression profiling of the rat brain during the first 24 h after experimental stroke identifies dynamic ischemia-induced gene expression patterns, and reveals a biphasic activation of genes in surviving tissue

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2005.03508.x ◽

2006 ◽

Vol 96 (1) ◽

pp. 14-29 ◽

Cited By ~ 60

Author(s):

Mattias Rickhag ◽

Tadeusz Wieloch ◽

Gunilla Gido ◽

Eskil Elmer ◽

Morten Krogh ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Rat Brain ◽

Expression Profiling ◽

Expression Patterns ◽

Experimental Stroke ◽

Gene Expression Patterns ◽

Temporal Gene Expression

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Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming

10.1101/710210 ◽

2019 ◽

Cited By ~ 3

Author(s):

Yuancheng Lu ◽

Anitha Krishnan ◽

Benedikt Brommer ◽

Xiao Tian ◽

Margarita Meer ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Vision Loss ◽

Ganglion Cells ◽

Expression Patterns ◽

The Body ◽

Gene Expression Patterns ◽

Nerve Crush ◽

Dna Methylation Age ◽

Methylation Patterns

Ageing is a degenerative process leading to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise, which disrupts youthful gene expression patterns that are required for cells to function optimally and recover from damage1–3. Changes to DNA methylation patterns over time form the basis of an ‘ageing clock’4, 5, but whether old individuals retain information to reset the clock and, if so, whether this would improve tissue function is not known. Of all the tissues in the body, the central nervous system (CNS) is one of the first to lose regenerative capacity6, 7. Using the eye as a model tissue, we show that expression of Oct4, Sox2, and Klf4 genes (OSK) in mice resets youthful gene expression patterns and the DNA methylation age of retinal ganglion cells, promotes axon regeneration after optic nerve crush injury, and restores vision in a mouse model of glaucoma and in normal old mice. This process, which we call recovery of information via epigenetic reprogramming or REVIVER, requires the DNA demethylases Tet1 and Tet2, indicating that DNA methylation patterns don’t just indicate age, they participate in ageing. Thus, old tissues retain a faithful record of youthful epigenetic information that can be accessed for functional age reversal.

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Pseudo-Location: A novel predictor for predicting pseudo-temporal gene expression patterns using spatial functional regression

10.1101/2020.06.11.145565 ◽

2020 ◽

Author(s):

Kyungmin Ahn ◽

Hironobu Fujiwara

Keyword(s):

Gene Expression ◽

Expression Patterns ◽

Gene Expression Patterns ◽

Functional Regression ◽

Rna Seq ◽

Temporal Gene Expression ◽

Early Stages ◽

The Future

Statement of withdrawalThe authors have withdrawn version 1 of this manuscript because a draft manuscript, which was still in the early stages of preparation and required major revisions including the replacement of the source RNA-seq datasets, was erroneously submitted. The authors do not wish this version to be cited as reference for this study. We will post a revised manuscript in the future. If you have any questions, please contact the corresponding author.

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