Entrapment prevents healing | Science

Fluorescent microscopy image of retinal tissue showing optic nerve fibers (red) connecting to retinal ganglion neurons (orange)

IMAGE: SCIMAT/SCIENCE SOURCE

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Fluorescent microscopy image of retinal tissue showing optic nerve fibers (red) connecting to retinal ganglion neurons (orange)

IMAGE: SCIMAT/SCIENCE SOURCE

Adult nerves usually fail to regenerate after injury. This is also true for the retinal ganglion cells (RGCs) that communicate visual information from the retina to the brain. Working with adult mice and cultured RGCs, Hilla et al. discovered a role for the chemokine receptor CXCR4 and its ligand, CXCL12, in reducing the ability of RGCs to successfully reconnect to the optic nerve. RGCs transport CXCL12 along their axons, which if cut, release the cytokine at the damage site. This in turn attracts other growing RGC axons to the injury site, functionally trapping them in the lesion and preventing them from re-establishing contact beyond the lesion site. Reducing the expression levels of either the receptor or the cytokine reduces the diversion of growing axons and promotes long-distance regeneration. Thus, targeting this pathway could potentially help with functional recovery after nerve injury.

Proc. Natl. Acad. Sci. U.S.A. 118, e2016409118 (2021).

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