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Subspecialties Retina, Basic & Translational Research, Neuro-ophthalmology

You Down with 4-AP?

Myelin is a wonderful mixture of proteins and lipids – the mere fact that oligodendrocytes (in the central nervous system) and Schwann cells (in the peripheral nervous system) wrap axons in myelin means that neural signaling can propagate speedily over far greater distances than is possible in their unmyelinated counterparts. What’s interesting is that today, in mice, it’s possible (with the right cocktail of neurotrophic factors) to regrow damaged optic nerve fibers – but to get them to function requires myelin – or, as it turns out, the presence of a voltage-gated K+ channel blocker like 4-aminopyridine (4-AP).

Fengfeng Bei, Henry Hing Cheong Lee and colleagues (1) are able regrow optic nerve fibers in mice with transected optic nerve tracts – either by deleting the PTEN and SOCS3 genes, or by overexpressing osteopontin (OPN), insulin-like growth factor-1 (IGF-1) and ciliary neurotrophic factor (CNTF) genes (Figure 1). Either approach achieves the same feat: retinal nerves that grow toward and terminate in the superior colliculus of the brain, forming functional synapses when they get there. The problem is, they don’t restore any semblance of visual acuity. Why? No signal reaches there, because of a lack of myelination.

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