Abstract
Purpose::
Electrical stimulation has been shown to promote axonal regeneration by purified retinal ganglion cells (RGC) via upregulation of BDNF and trkB mRNA. However, whether electrical stimulation promotes in vivo axonal regeneration by central nervous system neurons such as RGC remains unclear. We examined this possibility in a rat optic nerve crush injury model.
Methods::
Immediately after crushing the left optic nerve (ON) in rats, transcorneal electrical stimulation (TES) with biphasic current pulses (1 ms/phase, 100 µA, 20 Hz) was done for 1 hour via a contact lens electrode using four different protocols: once immediately after ON crush on day 0 (1×), twice on days 0 and 7 (2×), four times on days 0, 3, 6, and 10 (4×), and daily application (days 0-10). On day 12, 1% cholera toxin B subunit (CTB) was injected intraocularly for anterograde labeling of RGC axons and immunohistochemistry was done. Under a fluorescent microscope, we counted CTB-labeled axons at 250, 500, and 1,000 µm from the crush site.
Results::
The mean ± SD number of CTB-labeled axons at 250 µm from the crush site increased with the frequency of TES: [2.62 ± 0.25 (sham), 3.94 ± 0.54 (1×), 4.25 ± 1.19 (2×), 5.18 ± 0.99 (4×), and 5.94 ± 0.9 (daily). Only daily TES significantly increased the mean number of CTB-labeled axons compared with sham stimulation (p<0.05).
Conclusions::
TES promotes regeneration of crushed RGC axons in adult mammals, indicating that electrical activity may be important for RGC axonal regeneration in vivo.
Keywords: optic nerve • regeneration • electrophysiology: non-clinical