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Electrical activity has previously been demonstrated to be critical for enhancing retinal ganglion cells' responsiveness to trophic factors, survival, axon growth, and regeneration (Neuron 21, 681; Neuron 23, 285; Neuron 33, 689). Electrical activity may work through calcium entry, cyclic-AMP elevation, and subsequent downstream signaling. Providing exogenous electrical activity may make up for an inadequate level of such signaling after injury, for example in optic nerve trauma, stroke, or degenerative diseases like glaucoma. But how can we translate these findings to human trials, and provide such activity to RGCs in a safe fashion?
Morimoto et al. (399) have published a series of papers using transcorneal electrical stimulation in rodents and humans. In the current manuscript, they detail a careful study of the specific electrical parameters that, at least for the rat, optimally promote RGC survival after optic nerve crush. They demonstrate a beautiful dose-dependency of the electrical stimulation's pulse duration, frequency, and intensity, examining multiple features of each of these parameters.
The time point after injury that they focused on ‐ seven days ‐ is quite early in the process of RGC death after nerve crush, and it is possible that the optimal parameters for longer term survival will differ from those optimal for these short term results. We also cannot be sure that these specific parameters will translate to the human eye. Nevertheless, it would be exciting to see these and other investigators capitalize on their combined human and animal research data to construct a properly designed clinical trial examining transcorneal electrical stimulation as a method for RGC neuroprotection in human diseases such as glaucomas, and other optic neuropathies.