Regeneration of Axons in the Mammalian Visual System

Berry, Martin; Rees, L.; Sievers, Jobst

doi:10.1007/978-3-642-70699-8_3

Cited by 101 publications

(140 citation statements)

References 32 publications

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“…One widely studied model of regenerative failure of axons in the CNS is the optic nerve (Berry et al, 2008). Although mature RGCs do not normally regenerate axons, they enter into an active regenerative state after lens injury and subsequently regrow axons over considerable distances into the lesioned optic nerve (Fischer et al, 2000(Fischer et al, , 2008Leon et al, 2000;Lorber et al, 2005;Pernet and Di Polo, 2006).…”

Section: Discussionmentioning

confidence: 99%

Taxol Facilitates Axon Regeneration in the Mature CNS

Sengottuvel¹,

Leibinger²,

Pfreimer³

et al. 2011

J. Neurosci.

231

205

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Mature retinal ganglion cells (RGCs) cannot normally regenerate axons into the injured optic nerve but can do so after lens injury. Astrocyte-derived ciliary neurotrophic factor and leukemia inhibitory factor have been identified as essential key factors mediating this effect. However, the outcome of this regeneration is still limited by inhibitors associated with the CNS myelin and the glial scar. The current study demonstrates that Taxol markedly enhanced neurite extension of mature RGCs and PC12 cells by stabilization of microtubules and desensitized axons toward myelin and chondroitin sulfate proteoglycan (CSPG) inhibition in vitro without reducing RhoA activation. In vivo, the local application of Taxol at the injury site of the optic nerve of rats enabled axons to regenerate beyond the lesion site but did not affect the intrinsic regenerative state of RGCs. Furthermore, Taxol treatment markedly increased lens injury-mediated axon regeneration in vivo, delayed glial scar formation, suppressed CSPG expression, and transiently reduced the infiltration of macrophages at the injury site. Thus, microtubule-stabilizing compounds such as Taxol might be promising candidates as adjuvant drugs in the treatment of CNS injuries particularly when combined with interventions stimulating the intrinsic regenerative state of neurons.

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Section: Discussionmentioning

confidence: 99%

Taxol Facilitates Axon Regeneration in the Mature CNS

Sengottuvel¹,

Leibinger²,

Pfreimer³

et al. 2011

J. Neurosci.

231

205

View full text Add to dashboard Cite

show abstract

“…THE ASSERTION THAT mammalian central nervous system (CNS) axons do not regenerate after injury (1) must now be revised as new findings demonstrate the induction of substantial regrowth of axons after the administration of neurotrophins and inflammatory cytokines (2), and the activation of the mTOR pathway (3)(4)(5)(6). Remarkably, $100% of CNS axons of lower vertebrates spontaneously regenerate, reconnect synaptically with their targets and, usually within 1 month of injury, re-establish former function normally, as demonstrated by Sperry in his classic experiments in anuran, amphibian (7,8), and fish optic nerve (ON) (9) after transection.…”

mentioning

confidence: 99%

Axonal tracing of the normal and regenerating visual pathway of mouse, rat, frog, and fish using manganese‐enhanced MRI (MEMRI)

Sandvig

Berry

et al. 2011

Magnetic Resonance Imaging

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Purpose: To assess optic nerve (ON) regeneration after injury by applying manganese-enhanced MRI (MEMRI) in a study of comparative physiology between nonregenerating rat and mouse species and regenerating frog and fish species. Materials and Methods:The normal visual projections of rats, mice, frogs, and fish was visualized by intravitreal MnCl 2 injection followed by MRI. Rats and mice with ON crush (ONC) were divided into nonregenerating (ONC only), and regenerating animals with peripheral nerve graft (ONCþPNG; rats) or lens injury (ONCþLI; mice) and monitored by MEMRI at 1 and 20 days post-lesion (dpl). Frog and fish with ON transection (ONT) were monitored by MEMRI up to 6 months postlesion (mpl).Results: Signal intensity profiles of the Mn 2þ -enhanced ON were consistent with ON regeneration in the ONCþPNG and ONCþLI rat and mice groups, respectively, compared with the nonregenerating ONC groups. Furthermore, signal intensity profiles of the Mn 2þ -enhanced ON obtained between 1 mpl and 6 mpl in the fish and frog groups, respectively, were consistent with spontaneous, complete ON regeneration.Conclusion: Taken together, these results demonstrate that MEMRI is a viable method for serial, in vivo monitoring of normal, induced, and spontaneously regenerating optic nerve axons in different species.

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“…A combination of inhibitory molecules in the optic nerve (Berry et al, 2008), insufficient neurotrophic factors available to promote axon growth (Aguayo et al, 1996), and a decreased intrinsic regenerative capacity of retinal ganglion cells after an early period of developmental growth (Liu et al, 2011) all contribute to regenerative failure, but overcoming these alone or in combination enhances regenerative ability (Benowitz & Yin, 2007). A major question remains as to whether retinal ganglion cells derived from stem cells will also need to be treated to overcome these barriers to optic nerve axon growth and reconnection to the brain.…”

Section: Stem Cell Research and Opportunitiesmentioning

confidence: 99%