期刊论文详细信息
BMC Neuroscience
Retinal ganglion cell survival and axon regeneration in WldS transgenic rats after optic nerve crush and lens injury
Keith R Martin3  Marilita M Moschos1  Natalie D Bull2  Alessia Tassoni2  Barbara Lorber2 
[1] First Department of Ophthalmology, Evgenidion Hospital, University of Athens, Athens, Greece;Centre for Brain Repair, University of Cambridge, Cambridge, UK;Cambridge Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, United Kingdom
关键词: Activated retinal glia;    Survival;    Axon regeneration;    Retinal ganglion cell;    Slow Wallerian degeneration mutation;   
Others  :  1170702
DOI  :  10.1186/1471-2202-13-56
 received in 2011-12-02, accepted in 2012-06-06,  发布年份 2012
PDF
【 摘 要 】

Background

We have previously shown that the slow Wallerian degeneration mutation, whilst delaying axonal degeneration after optic nerve crush, does not protect retinal ganglion cell (RGC) bodies in adult rats. To test the effects of a combination approach protecting both axons and cell bodies we performed combined optic nerve crush and lens injury, which results in both enhanced RGC survival as well as axon regeneration past the lesion site in wildtype animals.

Results

As previously reported we found that the WldS mutation does not protect RGC bodies after optic nerve crush alone. Surprisingly, we found that WldS transgenic rats did not exhibit the enhanced RGC survival response after combined optic nerve crush and lens injury that was observed in wildtype rats. RGC axon regeneration past the optic nerve lesion site was, however, similar in WldS and wildtypes. Furthermore, activation of retinal glia, previously shown to be associated with enhanced RGC survival and axon regeneration after optic nerve crush and lens injury, was unaffected in WldS transgenic rats.

Conclusions

RGC axon regeneration is similar between WldS transgenic and wildtype rats, but WldS transgenic rats do not exhibit enhanced RGC survival after combined optic nerve crush and lens injury suggesting that the neuroprotective effects of lens injury on RGC survival may be limited by the WldS protein.

【 授权许可】

   
2012 Lorber et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150417024145300.pdf 2174KB PDF download
Figure 3. 110KB Image download
Figure 2. 80KB Image download
Figure 1. 115KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】
  • [1]Berry M, Carlile J, Hunter A: Peripheral nerve explants grafted into the vitreous body of the eye promote the regeneration of retinal ganglion cell axons severed in the optic nerve. J Neurocytol 1996, 25:147-170.
  • [2]Leon S, Yin Y, Nguyen J, Irwin N, Benowitz LI: Lens injury stimulates axon regeneration in the mature rat optic nerve. J Neurosci 2000, 20:4615-4626.
  • [3]Fischer D, Pavlidis M, Thanos S: Cateractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture. Invest Ophthalmol & Vis Sci 2000, 41:3943-3954.
  • [4]Lorber B, Berry M, Logan A: Different factors promote axonal regeneration of adult rat retinal ganglion cells after lens injury and intravitreal peripheral nerve grafting. J Neurosci Res 2008, 86:894-903.
  • [5]Lorber B, Berry M, Douglas MR, Nakazawa T, Logan A: Activated retinal glia promote neurite outgrowth of retinal ganglion cells via apolipoprotein E. J Neurosci Res 2009, 87:2645-2652.
  • [6]Yin Y, Henzl MT, Lorber B, Nakazawa T, Thomas TT, Jiang F, Langer R, Benowitz LI: Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nature Neurosci 2006, 9:843-852.
  • [7]Yin Y, Cui Q, Gilbert HY, Yang Y, Yang Z, Berlinicke C, Li Z, Zaverucha-do-Valle C, He H, Petkova V, Zack DJ, Benowitz LI: Oncomodulin links inflammation to optic nerve regeneration. Proc Natl Acad Sci USA 2009, 106:19587-19592.
  • [8]Müller A, Hauk TG, Fischer D: Astrocyte-derived CNTF switches mature RGCs to a regenerative state following inflammatory stimulation. Brain 2007, 130:3308-3320.
  • [9]Hauk TG, Müller A, Lee J, Schwendener R, Fischer D: Neuroprotective and axon growth promoting effects of intraocular inflammation do not depend on oncomodulin or the presence of large numbers of activated macrophages. Exp Neurol 2008, 209:469-482.
  • [10]Beirowski B, Babetto E, Coleman MP, Martin KR: The WldS gene delays axonal but not somatic degeneration in a rat glaucoma model. Eur J Neurosci 2008, 28:1166-1179.
  • [11]Lunn ER, Perry VH, Brown MC, Rosen H, Gordon S: Absence of Wallerian degeneration does not hinder regeneration in the peripheral nerve. Eur J Neurosci 1989, 1:27-33.
  • [12]Perry VH, Brown MC, Lunn ER: Very slow retrograde and Wallerian Degeneration in the CNS of C57BL/Ola Mice. Eur J Neurosci 1991, 3:102-105.
  • [13]Benavides E, Alvarez J: Peripheral axons of Wlds mice, which regenerate after a delay of several weeks, do so readily when transcription is inhibited in the distal stump. Neurosci Lett 1998, 258:77-80.
  • [14]Brown MC, Perry VH, Hunt SP, Lapper SR: Further studies on motor and sensory nerve regeneration in mice with delayed Wallerian degeneration. Eur J Neurosci 1994, 6:420-428.
  • [15]Bull ND, Johnson TV, Welsapar G, DeKorver NW, Tomarev SI, Martin KR: Use of an adult rat retinal explant model for screening of potential retinal ganglion cell neuroprotective therapies. Invest Ophthalmol Vis Sci 2011, 52:3309-3320.
  • [16]Elshatory Y, Deng M, Xie X, Gan L: Expression of the LIM-homeodomain protein Isl1 in the developing and mature mouse retina. J Comp Neurol 2007, 503:182-197.
  • [17]Osborne NN, Perry VH: Effect of neonatal ON transection on some classes of amacrine cells in the rat retina. Brain Res 1985, 343:230-235.
  • [18]Kielczewski JL, Pease ME, Quigley HA: The effect of experimental glaucoma and ON transection on amacrine cells in the rat retina. Invest Ophthalmol Vis Sci 2005, 46:3188-3196.
  • [19]Zhang Z, Guth L, Steward O: Mechanisms of motor recovery after subtotal spinal cord injury: Insights from the study of mice carrying a mutation (Wlds) that delays cellular responses to injury. Exp Neurol 1998, 149:221-229.
  • [20]Adalbert R, Gillingwater TH, Haley JE, Bridge K, Beirowski B, Berek L, Wagner D, Grumme D, Thomson D, Celik A, Addicks K, Ribchester RR, Coleman MP: A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses. Eur J Neurosci 2005, 21:271-277.
  • [21]Zurn AD, Bandtlow CE: Regeneration failure in the CNS: Cellular and Molecular Mechanisms. Adv Exp Med Biol 2006, 557:54-76.
  • [22]Berry M, Ahmed Z, Lorber B, Douglas M, Logan A: Regeneration of axons in the visual system. Restor Neurol Neurosci 2008, 26:147-174.
  • [23]Harvey AR, Hu Y, Leaver SG, Mellough CB, Park K, Verhaagen J, Plant GW, Cui Q: Gene therapy and transplantation in CNS repair: the visual system. Prog Retin Eye Res 2006, 25:449-489.
  • [24]Pernet V, Di Polo A: Synergistic action of brain-derived neurotrophic factor and lens injury promotes retinal ganglion cell survival, but leads to optic nerve dystrophy in vivo. Brain 2006, 129:1014-1026.
  • [25]Adalbert R, Nogradi A, Szabo A, Coleman MP: The slow Wallerian degeneration gene in vivo protects motor axons but not their cell bodies after avulsion and neonatal axotomy. Eur J Neurosci 2006, 24:2163-2168.
  • [26]Gillingwater TH, Haley JE, Ribchester RR, Horsburgh K: Neuroprotection after transient global cerebral ischemia in Wld(s) mutant mice. J Cereb Blood Flow Metab 2004, 24:62-66.
  • [27]Feng Y, Yan T, He Z, Zhai Q: Wld(S), Nmnats and axon degeneration–progress in the past two decades. Protein Cell 2010, 1:237-245.
  • [28]Antenor-Dorsey JA, O'Malley KL: WldS but not Nmnat1 protects dopaminergic neurites from MPP + neurotoxicity. Mol Neurodegener 2012, 7:5. BioMed Central Full Text
  • [29]Gillingwater TH, Wishart TM, Chen PE, Haley JE, Robertson K, MacDonald SH, Middleton S, Wawrowski K, Shipston MJ, Melmed S, Wyllie DJ, Skehel PA, Coleman MP, Ribchester RR: The neuroprotective WldS gene regulates expression of PTTG1 and erythroid differentiation regulator 1-like gene in mice and human cells. Hum Mol Genet 2006, 15:625-635.
  • [30]Wishart TM, Pemberton HN, James SR, McCabe CJ, Gillingwater TH: Modified cell cycle status in a mouse model of altered neuronal vulnerability (slow Wallerian degeneration; Wlds). Genome Biol 2008, 9:R101. BioMed Central Full Text
  • [31]Fang C, Bernardes-Silva M, Coleman MP, Perry VH: The cellular distribution of the Wlds chimeric protein and its constituent proteins in the CNS. Neurosci 2005, 135:1107-1118.
  • [32]Bignami A, Dahl D: The astroglial response to stabbing, Immunofluorescence studies with antibodies to astrocyte-specific protein (GFA) in mammalian and submammalian vertebrates. Neuropathol Appl Neurobiol 1976, 2:99-110.
  • [33]Schaden H, Stürmer CA, Bähr M: GAP-43 immunoreactivity and axon regeneration in retinal ganglion cells of the rat. J Neurobiol 1994, 25:1570-1578.
  • [34]Benowitz LI, Apostolides PJ, Perrone-Bizzozero N, Finklestein SP, Zwiers H: Anatomical distribution of the growth-associated protein GAP-43/B-50 in the adult rat brain. J Neurosci 1988, 8:339-352.
  文献评价指标  
  下载次数:39次 浏览次数:21次