scholarly journals Combined inhibition of apoptosis and necrosis promotes transient neuroprotection of retinal ganglion cells and partial-axon regeneration after optic nerve damage

2018 ◽  
Author(s):  
Maki Kayama ◽  
Kumiko Omura ◽  
Yusuke Murakami ◽  
Edith Reshef ◽  
Aristomenis Thanos ◽  
...  
Keyword(s):  
Cell Death ◽  
Optic Nerve ◽  
Axonal Regeneration ◽  
Axon Regeneration ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Interacting Protein ◽  
Caspase Inhibition ◽  
Apoptosis And Necrosis

SUMMARYRetinal ganglion cell (RGC) death is the hallmark of glaucoma. Axonal injury is thought to precede RGC loss in glaucoma, and thus studies using an optic nerve (ON) crush model have been widely used to investigate mechanisms of cell death that are common to both conditions. Prior work has focused on the involvement of caspases in RGC death, but little is known about the contribution of other forms of cell death such as necrosis. In this study we show that receptor interacting protein (RIP) kinase-mediated necrosis normally plays a role in RGC death and acts in concert with caspase-dependent apoptosis. The expression of RIP3, a key activator of RIP1 kinase, as well as caspase activity, increased following ON injury. Caspase inhibition alone failed to provide substantial protection to injured RGCs and unexpectedly exacerbated necrosis. In contrast, pharmacologic or genetic inhibition of RIP kinases in combination with caspase blockade delayed both apoptotic and necrotic RGC death, although RGCs still continued to die. Furthermore, inhibition of RIP1 kinase promoted a moderate level of axon regeneration that was only minimal affected by caspase inhibition. In conclusion, multiple approaches are required for effective RGC death prevention and axonal regeneration. Further studies are needed to elucidate more effective long term strategies that can lead to sustained neuroprotection and regeneration.

Long-term survival and axonal regeneration of retinal ganglion cells after optic nerve transection and a peripheral nerve graft

Neuroreport ◽  
2012 ◽  
Vol 23 (11) ◽  
pp. 692-697 ◽  
Author(s):  
Ling-Ping Cen ◽  
Jian-Min Luo ◽  
Yiqun Geng ◽  
Mingzhi Zhang ◽  
Chi Pui Pang ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Axonal Regeneration ◽  
Ganglion Cells ◽  
Nerve Graft ◽  
Retinal Ganglion ◽  
Nerve Transection ◽  
Term Survival ◽  
Peripheral Nerve Graft

scholarly journals Fish optic nerve oligodendrocytes support axonal regeneration of fish and mammalian retinal ganglion cells

Glia ◽  
1993 ◽  
Vol 8 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Martin Bastmeyer ◽  
Mathias Bähr ◽  
Claudia A. O. Stuermer
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Axonal Regeneration ◽  
Ganglion Cells ◽  
Retinal Ganglion

A second episode of ganglion cell death takes place when an optic nerve regenerates for a second time in the frog

1993 ◽  
Vol 10 (2) ◽  
pp. 297-301 ◽  
Author(s):  
L. D. Beazley ◽  
J.E. Darby
Keyword(s):  
Cell Death ◽  
Optic Nerve ◽  
Ganglion Cell ◽  
Ganglion Cells ◽  
Cresyl Violet ◽  
Retinal Ganglion ◽  
Nerve Crush ◽  
Optic Nerve Regeneration ◽  
Ability To Regenerate ◽  
Ganglion Cell Death

AbstractWe have previously reported that during optic nerve regeneration in the frog, 30–40% of retinal ganglion cells die, the loss being complete within 10 weeks. In the present study, we crushed the optic nerve, waited 10 weeks, and then recrushed the nerve at the same site. Retinae were examined 10 weeks later. We estimated ganglion cell numbers from cresyl-violet-stained wholemounts and found a fall of 53% compared to normals. The loss was significantly greater than the losses of 36% and 35%, respectively, in frogs which received a single optic nerve crush and were examined 10 or 20–24 weeks later. The results indicate that a second episode of ganglion cell death took place when the optic nerve regenerated a second time. We conclude that ganglion cells in the frog are not comprised of two subpopulations, only one of which intrinsically possesses the ability to regenerate.

scholarly journals Axonal regeneration of retinal ganglion cells after optic nerve pre-lesions and attachment of normal or pre-degenerated peripheral nerve grafts

2002 ◽  
Vol 19 (5) ◽  
pp. 661-668 ◽  
Author(s):  
SI-WEI YOU ◽  
KULDIP S. BEDI ◽  
HENRY K. YIP ◽  
KWOK-FAI SO
Keyword(s):  
Optic Nerve ◽  
Peripheral Nerve ◽  
Retinal Ganglion Cells ◽  
Axonal Regeneration ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Lesion Effect ◽  
Nerve Grafts ◽  
Proximal Lesion ◽  
Peripheral Nerve Grafts

Axonal regeneration of retinal ganglion cells (RGCs) into a normal or pre-degenerated peripheral nerve graft after an optic nerve pre-lesion was investigated. A pre-lesion performed 1–2 weeks before a second lesion has been shown to enhance axonal regeneration in peripheral nerves (PN) but not in optic nerves (ON) in mammals. The lack of such a beneficial pre-lesion effect may be due to the long delay (1–6 weeks) between the two lesions since RGCs and their axons degenerate rapidly 1–2 weeks following axotomy in adult rodents. The present study examined the effects of the proximal and distal ON pre-lesions with a shortened delay (0–8 days) on axonal regeneration of RGCs through a normal or pre-degenerated PN graft. The ON of adult hamsters was transected intraorbitally at 2 mm (proximal lesion) or intracranially at 7 mm (distal lesion) from the optic disc. The pre-lesioned ON was re-transected at 0.5 mm from the disc after 0, 1, 2, 4, or 8 days and a normal or a pre-degenerated PN graft was attached onto the ocular stump. The number of RGCs regenerating their injured axons into the PN graft was estimated by retrograde labeling with FluoroGold 4 weeks after grafting. The number of regenerating RGCs decreased significantly when the delay-time increased in animals with both the ON pre-lesions (proximal or distal) compared to control animals without an ON pre-lesion. The proximal ON pre-lesion significantly reduced the number of regenerating RGCs after a delay of 8 days in comparison with the distal lesion. However, this adverse effect can be overcome, to some degree, by a pre-degenerated PN graft applied 2, 4, or 8 days after the distal ON pre-lesion enhanced more RGCs to regenerate than the normal PN graft. Thus, in order to obtain the highest number of regenerating RGCs, a pre-degenerated PN should be grafted immediately after an ON lesion.

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