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New Optic Nerve?
Jonathan Crowston, Robert N. Weinreb
Among the nominated papers (see page 9) was one by R.G. Ellis-Behnke et al. on nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision. PNAS 2006 5054-5059. This study rightly received praise from the nominating Glaucoma Societies. Its usefulness for the treatment of glaucoma is discussed in the following comments.
Jonathan Crowston
Axon regeneration in the optic nerve remains one of the holy grails
of glaucoma research. Ellis-Behnke and colleagues provide convincing data
in this PNAS manuscript to support the feasibility of optic nerve axon regeneration
and the restoration of functional vision in the hamster after optic nerve
transection.
Injection of a self assembling peptide nanofiber at the site of acute optic nerve transection stimulated axonal regeneration and re-con-necton in 92% of treated eyes. Importantly, this was associated with the return of functional vision in 75% of treated eyes. No axon regeneration or vision restoration was seen in any of the saline injected controls. The injected nanofiber solution appeared to be biocompatible and did not lead to any obvious systemic side effects.
Similar regeneration has been previously reported using sciatic peripheral nerve grafts. However, this novel approach using nano-technology may obviate the need to transplant autologous peripheral nerve tissue limiting the potential for associated loss of function of the operated limb.
This impressive study is augmented by convincing video footage posted online that demonstrates the restoration of functional vision in the injected hamsters.
Although acute nerve transection may lend itself more easily to axonal regeneration compared to chronic loss over a considerable amount of time (as occurs in glaucoma). These important experiments demonstrate that given the right milieu, the optic nerve and CNS can be made to regenerate. This gives hope to the notion that glaucomatous optic nerves can be reconstituted.
Robert N. Weinreb
The potential of exploiting this emerging technology to repair optic
nerve injury and restore vision in glaucoma is enormous. Many of the biological
events that are initiated by the acute injury of optic nerve transection
are similar to those observed in experimental ocular hypertensive glaucoma
and human glaucoma. With experimental ocular hypertensive glaucoma, as observed
in the laser-treated monkey model, the effects of acute injury caused by
the sudden increase in intraocular pressure are superimposed on a chronic
course. Acute injury superimposed on chronic injury also may occur in some,
if not many, patients with primary open angle glaucoma. Moreover, there
may be a blockade of target-derived (from the lateral geniculate nucleus)
neurotrophic factors with both experimental ocular hyper-tensive glaucoma
and human glaucoma, as occurs with optic nerve transection. In the future,
it is entirely plausible that glaucoma management will consist not only
of preventing retinal ganglion cell injury and preserving their function,
but also repairing and restoring both their structure and function.
