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Glaucoma Dialogue IGR 11-2

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Comment by Manuel Vidal-Sanz & James Morgan on:

23848 Axonal regeneration induced by repetitive electrical stimulation of crushed optic nerve in adult rats, Tagami Y; Kurimoto T; Miyoshi T et al., Japanese Journal of Ophthalmology, 2009; 53: 257-266

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This paper addresses the issue of axon regeneration in the optic nerve following ON crush and the application of transcorneal stimulation to stimulate the crushed optic nerve.
Conventional anterograde and retrograde axon tracing techniques were used in an optic nerve crush paradigm. Insulin-like growth factor (IGF) was singled out, on the basis of a literature review, as a possible mediator of any protective effect that could result from electrical stimulation. The role of IGF in any regeneration was tested by the systemic administration of the inhibitor JB3. Evidence offered in support of axon regrowth was based on axon counts in the vicinity of the optic nerve crush.
There are several flaws with the paper which undermine the authors� conclusions. Since they did not report the presence of growth cones (which should move away from the crush site) it is not possible to conclude that regeneration has taken place. The only conclusion that can be drawn is that axon degeneration was delayed by the application of electrical stimulation and then only in small proportion of the axon population. The cells survival data are more convincing but the sample numbers are relatively small (n=6) and should be treated with caution. The role of IGF is also questionable. I would at least expect some Western blots to demonstrate up-regulation following stimulation.

The only conclusion that can be drawn is that axon degeneration was delayed by the application of electrical stimulation and then only in small proportion of the axon population

Electrical stimulation may well be beneficial in RGC preservation and axon outgrowth. One possible check on its role would be with the intraocular application of TTX, which should silence RGC activity and counteract the effect of electrical stimulation.
In summary, the study covers an interesting area but does not provide data in support of regeneration: even if regeneration were occurring it appears to be marginal and affects a small proportion of the axons. As it stands delayed axonal degeneration is a more pragmatic conclusion.

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