scholarly journals Prior Exposure to Immunosuppressors Sensitizes Retinal Microglia and Accelerates Optic Nerve Regeneration in Zebrafish

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Ilse Bollaerts ◽  
Jessie Van houcke ◽  
An Beckers ◽  
Kim Lemmens ◽  
Sophie Vanhunsel ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Inflammatory Response ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Molecular Mechanisms ◽  
Strong Positive Correlation ◽  
Cns Injury ◽  
Adult Zebrafish ◽  
Optic Nerve Regeneration ◽  
Retinal Microglia

As adult mammals lack the capacity to replace or repair damaged neurons, degeneration and trauma (and subsequent dysfunction) of the central nervous system (CNS) seriously constrains the patient’s life quality. Recent work has shown that appropriate modulation of acute neuroinflammation upon CNS injury can trigger a regenerative response; yet, the underlying cellular and molecular mechanisms remain largely elusive. In contrast to mammals, zebrafish retain high regenerative capacities into adulthood and thus form a powerful model to study the contribution of neuroinflammation to successful regeneration. Here, we used pharmacological immunosuppression methods to study the role of microglia/macrophages during optic nerve regeneration in adult zebrafish. We first demonstrated that systemic immunosuppression with dexamethasone (dex) impedes regeneration after optic nerve injury. Secondly, and strikingly, local intravitreal application of dex or clodronate liposomes prior to injury was found to sensitize retinal microglia. Consequently, we observed an exaggerated inflammatory response to subsequent optic nerve damage, along with enhanced tectal reinnervation. In conclusion, we found a strong positive correlation between the acute inflammatory response in the retina and the regenerative capacity of the optic nerve in adult zebrafish subjected to nerve injury.

Müller glia–myeloid cell crosstalk accelerates optic nerve regeneration in the adult zebrafish

Glia ◽  
2021 ◽  
Author(s):  
Annelies Van Dyck ◽  
Ilse Bollaerts ◽  
An Beckers ◽  
Sophie Vanhunsel ◽  
Nynke Glorian ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Regeneration ◽  
Myeloid Cell ◽  
Muller Glia ◽  
Müller Glia ◽  
Adult Zebrafish ◽  
Optic Nerve Regeneration ◽  
Cell Crosstalk

scholarly journals Topical ripasudil stimulates neuroprotection and axon regeneration in adult mice following optic nerve injury

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Euido Nishijima ◽  
Kazuhiko Namekata ◽  
Atsuko Kimura ◽  
Xiaoli Guo ◽  
Chikako Harada ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Actin Polymerization ◽  
Mitogen Activated Protein Kinase ◽  
Microtubule Assembly ◽  
Nerve Degeneration ◽  
Optic Nerve Injury ◽  
Optic Nerve Regeneration ◽  
Adult Mice

Abstract Optic nerve injury induces optic nerve degeneration and retinal ganglion cell (RGC) death that lead to visual disturbance. In this study, we examined if topical ripasudil has therapeutic potential in adult mice after optic nerve crush (ONC). Topical ripasudil suppressed ONC-induced phosphorylation of p38 mitogen-activated protein kinase and ameliorated RGC death. In addition, topical ripasudil significantly suppressed the phosphorylation of collapsin response mediator protein 2 and cofilin, and promoted optic nerve regeneration. These results suggest that topical ripasudil promotes RGC protection and optic nerve regeneration by modulating multiple signaling pathways associated with neural cell death, microtubule assembly and actin polymerization.

scholarly journals Time course Analysis of Gene expression patterns in ZebrafIsh Eye during Optic Nerve Regeneration

2010 ◽  
Vol 4 ◽  
pp. JEN.S5006 ◽  
Author(s):  
Amy T. Mccurley ◽  
Gloria V. Callard
Keyword(s):  
Gene Expression ◽  
Optic Nerve ◽  
Nerve Regeneration ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Neural Cells ◽  
Nerve Crush ◽  
Optic Nerve Regeneration

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.

scholarly journals Acute neuroinflammation mediates optic nerve regeneration in adult zebrafish

2015 ◽  
Vol 9 ◽  
Author(s):  
Bollaerts Ilse ◽  
Van Houcke Jessie ◽  
Beckers An ◽  
Lemmens Kim ◽  
Van Hove Inge ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Regeneration ◽  
Adult Zebrafish ◽  
Optic Nerve Regeneration

INVESTIGATING CRMP4 FUNCTION IN NERVE REGENERATION

2008 ◽  
Vol 31 (4) ◽  
pp. 18
Author(s):  
S Ong Tone ◽  
Y Z Alabed ◽  
A Di Polo ◽  
A E Fournier
Keyword(s):  
Optic Nerve ◽  
Neurite Outgrowth ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Molecular Mechanisms ◽  
Ganglion Cells ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Growth State

Background: The failure of CNS neurons to spontaneously regenerate following injury can be partially attributed to the expression of neurite outgrowth inhibitory myelin associated inhibitors (MAIs). MAIs signal through a tripartite receptor complex to activate the cytosolic protein RhoA and influence cytoskeletal dynamics. RhoA antagonists promote neuronal survival and regeneration in animal models of nerve injury. However, RhoA's potential as a therapeutic target may be limited by its widespread roles in multiple cellular processes and cell types. In an attempt to discover more specific therapeutic targets to promote nerve regeneration, our lab identified the cytosolic phosphoprotein CRMP4b (Collapsin Response Mediator Protein 4b) as a protein that functionally interacts with RhoA to mediate neurite outgrowth inhibition. Blockade of the RhoA-CRMP4b interaction with a competitive peptide (C4RIP) attenuates myelin-dependent neurite outgrowth inhibition. Methods: We are currently investigating the in vivo roles of CRMP4in regeneration in an optic nerve injury model by developing a readily deliverable version of C4RIP. Results: Preliminary results suggest that overexpression of C4RIP in retinal ganglion cells by adeno-associated virus does not promote regeneration. However, studies investigating the ability of C4RIP to promote nerve regeneration into the optic nerve following stimulation of neurons into anactive growth state are currently in progress. Conclusion: Elucidating the role of CRMP4 in nerve regeneration may provide insight into the molecular mechanisms following nervous system injury and lead to the development of more specific therapeutic interventions. Reference: Alabed YZ, Pool M, Ong Tone S, Fournier AE.Identification of CRMP4 as a convergent regulator of axon outgrowth inhibition. J Neurosci 2007;27:1702-11.

A vulnerable period of colchicine toxicity during goldfish optic nerve regeneration

1999 ◽  
Vol 842 (1) ◽  
pp. 62-72 ◽  
Author(s):  
Joseph A Dybowski ◽  
Anne M Heacock ◽  
Bernard W Agranoff
Keyword(s):  
Optic Nerve ◽  
Nerve Regeneration ◽  
Optic Nerve Regeneration ◽  
Vulnerable Period

scholarly journals zRICH, a protein induced during optic nerve regeneration in zebrafish, promotes neuritogenesis and interacts with tubulin

2012 ◽  
Vol 1474 ◽  
pp. 29-39 ◽  
Author(s):  
Satya S. Pathi ◽  
Soumia Jose ◽  
Suman Govindaraju ◽  
Juan A. Conde ◽  
Hannah E. Romo ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Nerve Regeneration ◽  
Optic Nerve Regeneration
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