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Y. Tagami, T. Kurimoto, S. Oono, R. Kashimoto, T. Miyoshi, O. Mimura; Axonal Regeneration Induced by Daily Electrical Stimulation Is Probably Dependent on Igf-1 Activation in Adult Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2059. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We previously reported that transcorneal electrical stimulation (TES) enhances axonal regeneration of retinal ganglion cells (RGCs) of adult rats, and a daily application of TES gives better results. However, the mechanism for the TES enhancement is still unknown. The purpose of this study was to determine whether the axonal regeneration enhanced by TES is related to IGF-1 activation.
TES was applied for 1 hour immediately after the optic nerve crush (ONC). The TES parameters were; biphasic current pulses of 100 µA and 1 ms/phase at 20 Hz. A single TES immediately after ONC (day 0, single TES) or daily TES (day 0-12, daily TES) was performed. Axonal regeneration was determined by anterograde labeling of RGC axons. The number of labeled axons at 250, 500, and 1000 µm from the crush site was determined. To examine whether the axonal regeneration is mediated by IGF-1 receptors, we injected IGF-1 receptor antagonist, JB3, intraperitoneally before each TES application. Immunostaining for IGF-1 was performed to examine the effect of single and daily TES. To test the survival-promoting effects of daily TES, we determined the mean density of retrogradely-labeled RGCs on day 12 after ONC.
Daily TES significantly increased the mean number of labeled axons at only 250 µm (sham stimulation, 2.61±0.28; daily TES, 5.94±0.92, P<0.01). The injection of JB-3 before each TES decreased the mean number of labeled axons significantly (daily TES, 5.94±0.92; daily TES with JB3, 1.93±0.67, P<0.05). Daily TES increased the expression of IGF-1 significantly in the inner nuclear layer and ganglion cell layer on day 12. However, the level of IGF-1 after a single TES returned to the normal level. Daily TES significantly increased the mean densities of retrogradely-labeled RGCs compared to that without any applications. The injection of JB-3 before each TES did not significantly decrease the RGC survival.
Daily electrical stimulation promotes both the regeneration of axons and survival of RGC after ONC. Axonal regeneration is possibly dependent on the IGF-1 system, whereas the survival-promoting effect might be related to other molecules except IGF-1.
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