Abstract
Purpose
To investigate whether electrical stimulation promoted axonal regeneration of retinal ganglion cells (RGCs) after optic nerve (ON) crush in adult rats.
Methods
Transcorneal electrical stimulation (TES), which stimulates the retina with current from a corneal contact lens electrode, was used to stimulate the eye. TES was applied for 1 h immediately after ON crush. Axonal regeneration was determined by anterograde labeling of RGC axons. To examine whether the axonal regeneration was mediated by insulin-like growth factor 1 (IGF-1) receptors, an IGF-1 receptor antagonist, JB3, was injected intraperitoneally before each TES application. Immunostaining for IGF-1 was performed to examine the effects of TES. To test the survival-promoting effects of TES applied daily, the mean density of retrogradely labeled RGCs was determined on day 12 after ON crush.
Results
Compared with sham stimulation, the mean number of regenerating axons significantly increased at 250 μm distal from the lesion and increased IGF-1 immunoreactivity was observed in retinas treated daily with TES. Preinjection of an IGF-1 receptor antagonist significantly blocked axonal regeneration by TES applied daily. TES applied daily also markedly enhanced the survival of RGCs 12 days after ON crush.
Conclusion
TES applied daily promotes both axonal regeneration and survival of RGCs after ON crush.
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References
Zhou Q, Poo MM. Reversal and consolidation of activity-induced synaptic modifications. Trends Neurosci 2004;27:378–383.
Dan Y, Poo MM. Spike timing-dependent plasticity: from synapse to perception. Physiol Rev 2006;86:1033–1048.
Al-Majed AA, Neumann CM, Brushart TM, Gordon T. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J Neurosci 2000;20:2602–2608.
Wallace MC, Tator CH, Piper I. Recovery of spinal cord function induced by direct current stimulation of the injured rat spinal cord. Neurosurgery 1987;20:878–884.
Borgens RB, Blight AR, McGinnis ME. Behavior recovery induced by applied electric field after spinal cord hemisection in guinea pig. Science 1987;238:366–369.
Goldberg JL, Espinosa JS, Xu Y, et al. Retinal ganglion cells do not extend axons by default: promotion by neurotrophic signaling and electrical activity. Neuron 2002;33:689–702.
Morimoto T, Miyoshi T, Fujikado T, Tano Y, Fukuda Y. Electrical stimulation enhances the survival of axotomized retinal ganglion cells in vivo. Neuroreport 2002;13:227–230.
Okazaki Y, Morimoto T, Sawai H. Parameters of optic nerve electrical stimulation affecting neuroprotection of axotomized retinal ganglion cells in adult rats. Neurosci Res 2008;61:129–135.
Morimoto T, Miyoshi T, Matsuda S, et al. Transcorneal electrical stimulation rescues axotomized retinal ganglion cells by activating endogenous retinal IGF-1 system. Invest Ophthalmol Vis Sci 2005;46:2147–2155.
Morimoto T, Fujikado T, Choi JS, et al. Transcorneal electrical stimulation promotes the survival of photoreceptors and preserves retinal function in royal college of surgeons rats. Invest Ophthalmol Vis Sci 2007;48:4725–4732.
Vergani L, Di Giulio AM, Losa M, et al. Systemic administration of insulin-like growth factor decreases motor neuron cell death and promotes the muscle reinnervation. J Neurosci Res 1998;54:840–847.
Rind HB, von Bartheld CS. Target-derived cardiotrophin-1 and insulin-like growth factor-1 promote neurite growth and survival of developing oculomotor neurons. Mol Cell Neurosci 2002;19:58–71.
Xu QG, Li XQ, Kotecha SA, et al. Insulin as an in vivo growth factor. Exp Neurol 2004;188:43–51.
Homma K, Koriyama Y, Mawatari K, et al. Early downregulation of IGF-I decides the fate of rat retinal ganglion cells after optic nerve injury. Neurochem Int 2007;50:741–748.
Kurimoto T, Ishii M, Tagami Y, et al. Xylazine promotes axonal regeneration in the crushed optic nerve of adult rats. Neuroreport 2006;17:1525–1529.
Peinado-Rámon P, Salvador M, Villegas-Péres MP, Vidal-Sanz M. Effects of axotomy and intraocular administration of NT-4, NT-3, and brain-derived neurotrophic factor on the survival of adult rat retinal ganglion cells—a quantitative in vivo study. Invest Ophthalmol Vis Sci 1996;37:489–500.
Kashimoto R, Kurimoto T, Miyoshi T, et al. Cilostazol promotes survival of axotomized retinal ganglion cells in adult rats. Neurosci Lett 2008;436:116–119.
Pietrzkowski Z, Wernicke D, Porcu P, Jameson BA, Baserga R. Inhibition of cellular proliferation by peptide analogues of insulinlike growth factor 1. Cancer Res 1992;52:6447–6451.
Koriyama Y, Homma K, Sugitani K, et al. Upregulation of IGF-1 in the goldfish retinal ganglion cells during the early stage of optic nerve regeneration. Neurochem Int 2007;50:749–756.
Bonfanti L, Strettoi E, Chierzi S, et al. Protection of retinal ganglion cells from natural and axotomy-induced cell death in neonatal transgenic mice overexpressing bcl-2. J Neurosci 1996;16:4186–4194.
Chierzi S, Strettoi E, Cenni MC, Maffei L. Optic nerve crush: axonal responses in wild-type and bcl-2 transgenic mice. J Neurosci 1999;19:8367–8376.
Inoue T, Hosokawa M, Morigiwa K, Ohashi Y, Fukuda Y. Bcl-2 overexpression does not enhance in vivo axonal regeneration of retinal ganglion cells after peripheral nerve transplantation in adult mice. J Neurosci 2002;22:4468–4477.
So KF, Aguayo AJ. Lengthy regrowth of cut axons from ganglion cells after peripheral nerve transplantation into the retina of adult rats. Brain Res 1985;328:349–354.
Villegas-Pérez MP, Vidal-Sanz M, Bray GM, Aguayo AJ. Influences of peripheral nerve grafts on the survival and regrowth of axotomized retinal ganglion cells in adult rats. J Neurosci 1988;8:265–280.
Lucius R, Gallint S, Rosenstiel P, et al. The angiotensin II type 2(AT2) receptor promotes axonal regeneration in the optic nerve of adult rats. J Exp Med 1998;188:661–670.
Lehmann M, Fournier A, Selles-Navarro I, et al. Inactivation of Rho signaling pathway promotes CNS axon regeneration. J Neurosci 1999;19:7537–7547.
Lingor P, Teusch N, Schwarz K, et al. Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo. J Neurochem 2007;103:181–189.
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.
Yin Y, Cui Q, Li Y, et al. Macrophage-derived factors stimulate optic nerve regeneration. J Neurosci 2003;23:2284–2293.
Yin Y, Henzl MT, Lorber B, et al. Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells. Nat Neurosci 2006;9:843–852.
Li Y, Sauvé Y, Li D, Lund RD, Raisman G. Transplanted olfactory ensheathing cells promote regeneration of cut adult rat optic nerve axons. J Neurosci 2003;23:7783–7788.
Fujikado T, Morimoto T, Matsushita K, et al. Effect of transcorneal electrical stimulation in patients with nonarteritic ischemic optic neuropathy or traumatic optic neuropathy. Jpn J Ophthalmol 2006;50:266–273.
Inomata K, Shinoda K, Ohde H, et al. Transcorneal electrical stimulation of retina to treat longstanding retinal artery occlusion. Graefes Arch Clin Exp Ophthalmol 2007;245:1773–1780.
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Tagami, Y., Kurimoto, T., Miyoshi, T. et al. Axonal regeneration induced by repetitive electrical stimulation of crushed optic nerve in adult rats. Jpn J Ophthalmol 53, 257–266 (2009). https://doi.org/10.1007/s10384-009-0657-8
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DOI: https://doi.org/10.1007/s10384-009-0657-8