Growth and pathfinding of regenerating axons in the optic projection of adult fish

Becker, Catherina G.; Becker, Thomas

doi:10.1002/jnr.21121

Cited by 61 publications

(59 citation statements)

References 44 publications

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“…To study remyelination, we aimed to produce a model of focal demyelination, with no or minimal axonal damage. The optic nerve is ideal for remyelination studies as it contains mostly myelinated axons, is easily accessible and has been used previously for investigation of axon regeneration [41,20]. We used the myelinotoxin LPC, as it has been used extensively in rodent models of demyelination (reviewed in [16]).…”

Section: Resultsmentioning

confidence: 99%

Zebrafish regenerate full thickness optic nerve myelin after demyelination, but this fails with increasing age

Münzel

Becker

et al. 2014

acta neuropathol commun

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Introduction: In the human demyelinating central nervous system (CNS) disease multiple sclerosis, remyelination promotes recovery and limits neurodegeneration, but this is inefficient and always ultimately fails. Furthermore, these regenerated myelin sheaths are thinner and shorter than the original, leaving the underlying axons potentially vulnerable. In rodent models, CNS remyelination is more efficient, so that in young animals (but not old) the number of myelinated axons is efficiently restored to normal, but in both young and old rodents, regenerated myelin sheaths are still short and thin. The reasons for these differences in remyelination efficiency, the thinner remyelinated myelin sheaths compared to developmental myelin and the subsequent effect on the underlying axon are unclear. We studied CNS remyelination in the highly regenerative adult zebrafish (Danio rerio), to better understand mechanisms of what we hypothesised would be highly efficient remyelination, and to identify differences to mammalian CNS remyelination, as larval zebrafish are increasingly used for high throughput screens to identify potential drug targets to improve myelination and remyelination. Results: We developed a novel method to induce a focal demyelinating lesion in adult zebrafish optic nerve with no discernible axonal damage, and describe the cellular changes over time. Remyelination is indeed efficient in both young and old adult zebrafish optic nerves, and at 4 weeks after demyelination, the number of myelinated axons is restored to normal, but internode lengths are short. However, unlike in rodents or in humans, in young zebrafish these regenerated myelin sheaths were of normal thickness, whereas in aged zebrafish, they were thin, and remained so even 3 months later. This inability to restore normal myelin thickness in remyelination with age was associated with a reduced macrophage/microglial response.

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Section: Resultsmentioning

confidence: 99%

Zebrafish regenerate full thickness optic nerve myelin after demyelination, but this fails with increasing age

Münzel

Becker

et al. 2014

acta neuropathol commun

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“…Functional regeneration of the fish retina occurs through progenitors derived from Müller glia [12][13][14][15] and possibly through the progenitors in the CGZ [15]. Retinal regeneration in fish has been the focus of several recent comprehensive reviews [16,17], and accordingly will not be discussed in depth here.…”

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confidence: 97%

Turning Müller Glia into Neural Progenitors in the Retina

Fischer

Bongini

2010

Mol Neurobiol

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Stimulating neuronal regeneration is a potential strategy to treat sight-threatening diseases of the retina. In some classes of vertebrates, retinal regeneration occurs spontaneously to effectively replace neurons lost to acute damage in order to restore visual function. There are different mechanisms and cellular sources of retinal regeneration in different species, include the retinal pigmented epithelium, progenitors seeded across the retina, and the Müller glia. This review briefly summarizes the different mechanisms of retinal regeneration in frogs, fish, chicks, and rodents. The bulk of this review summarizes and discusses recent findings regarding regeneration from Müller glia-derived progenitors, with emphasis on findings in the chick retina. The Müller glia are a promising source of regeneration-supporting cells that are intrinsic to the retina and significant evidence indicated these glias can be stimulated to produce neurons in different classes of vertebrates. The key to harnessing the neurogenic potential of Müller glia is to identify the secreted factors, signaling pathways, and transcription factors that enable de-differentiation, proliferation, and neurogenesis. We review findings regarding the roles of mitogen-activated protein kinase and notch signaling in the proliferation and generation of Müller glia-derived retinal progenitors.

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“…To make functionally meaningful connections with their target neurons, RGC axons have to follow the correct path. Evidence suggests that there is indeed appropriate expression of guidance cues that can be used by the regenerating axons (Becker and Becker 2007), which is also reflected by the observation that only little reinnervation errors are made . This is in contrast to the papers describing misguidance of induced axonal regeneration after ONC in rodents Pernet et al 2013a, b).…”

Section: Models and Methods To Study Spontaneous Optic Nerve Regeneramentioning

confidence: 95%

“…This is in contrast to the papers describing misguidance of induced axonal regeneration after ONC in rodents Pernet et al 2013a, b). RGC axons innervate different areas in the zebrafish brain, of which the optic tectum is the largest and by far the most studied target area in optic nerve regeneration research (Becker et al 2000;Becker and Becker 2007;Erskine and Herrera 2007). The first regenerating axons reach the optic tectum within the first week after injury (Kato et al 2013;Bhumika et al 2015).…”

Section: Models and Methods To Study Spontaneous Optic Nerve Regeneramentioning

confidence: 99%

Complementary research models and methods to study axonal regeneration in the vertebrate retinofugal system

et al. 2017

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Due to the lack of axonal regeneration, age-related deterioration in the central nervous system (CNS) poses a significant burden on the wellbeing of a growing number of elderly. To overcome this regenerative failure and to improve the patient's life quality, the search for novel regenerative treatment strategies requires valuable (animal) models and techniques. As an extension of the CNS, the retinofugal system, consisting of retinal ganglion cells that send their axons along the optic nerve to the visual brain areas, has importantly contributed to the current knowledge on mechanisms underlying the restricted regenerative capacities and to the development of novel strategies to enhance axonal regeneration. It provides an extensively used research tool, not only in amniote vertebrates including rodents, but also in anamniote vertebrates, such as zebrafish. Indeed, the latter show robust regeneration capacities, thereby providing insights into the factors that contribute to axonal regrowth and proper guidance, complementing studies in mammals. This review provides an integrative and critical overview of the classical and state-of-the-art models and methods that have been employed in the retinofugal system to advance our knowledge on the signaling pathways underlying the restricted versus robust axonal regeneration in rodents and zebrafish, respectively. In vitro, ex vivo and in vivo models and techniques to improve the visualization and analysis of regenerating axons are summarized. As such, the retinofugal system is presented as a valuable model to further facilitate research on axonal regeneration and to open novel therapeutic avenues for CNS pathologies.

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Growth and pathfinding of regenerating axons in the optic projection of adult fish

Cited by 61 publications

References 44 publications

Zebrafish regenerate full thickness optic nerve myelin after demyelination, but this fails with increasing age

Zebrafish regenerate full thickness optic nerve myelin after demyelination, but this fails with increasing age

Turning Müller Glia into Neural Progenitors in the Retina

Complementary research models and methods to study axonal regeneration in the vertebrate retinofugal system

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