Full-length axon regeneration in the adult mouse optic nerve and partial recovery of simple visual behaviors

Abstract

The mature optic nerve cannot regenerate when injured, leaving victims of traumatic nerve damage or diseases such as glaucoma with irreversible visual losses. Recent studies have identified ways to stimulate retinal ganglion cells to regenerate axons part-way through the optic nerve, but it remains unknown whether mature axons can reenter the brain, navigate to appropriate target areas, or restore vision. We show here that with adequate stimulation, retinal ganglion cells are able to regenerate axons the full length of the visual pathway and on into the lateral geniculate nucleus, superior colliculus, and other visual centers. Regeneration partially restores the optomotor response, depth perception, and circadian photoentrainment, demonstrating the feasibility of reconstructing central circuitry for vision after optic nerve damage in mature mammals.

NF-κB determines axonal re- and degeneration by cell-specific balance of RelA and p50 subunits in the adult CNS

“…S2; Haenold et al, 2012;Fischer et al, 2014). Ongoing long-term studies using repetitive MRI of the visual projection might delineate whether these axons become connected with midbrain targets (as recently claimed by Benowitz's group) in a manner dependent upon cAMP-and PTEN-regulated oncomodulin (De Lima et al, 2012).…”

Cell biology of spinal cord injury and repair

“…13, 15, 52, and Figure 1, A and B). Scar-forming astrocytes were long thought to be the primary cause for the failure of CNS axons to regenerate (53,54), but this notion is now strongly challenged by studies showing that appropriately stimulated CNS axons regenerate robustly in spite of astrocyte scar formation in optic nerve (45,47,55) and in spinal cord (19). Neither preventing astrocyte scar formation nor removing chronic astrocyte scars leads to spontaneous axon regeneration of descending motor, ascending sensory, or serotonin axons (19).…”

“…Current evidence suggests that neural connections could be reestablished by combination of local delivery of axon chemoattractive factors and a growth supportive matrix with activation of intrinsic neuronal growth programs. Various means of reactivating neuron-intrinsic growth programs are emerging, including modulating specific genetic pathways ( Figure 3A and discussed above), providing neuronal cell bodies with specific growth factors (150) or inflammatory factors (51,55,151), or stimulating neuronal activity (152). There is a growing list of chemoattractive growth factors that stimulate and guide regrowth of specific axons after SCI, including BDNF and NT3 for sensory axons (19,88), GDNF for propriospinal axons (89), and IGF1 for corticospinal axons (153), as well as pleotropic growth factors such as FGF and EGF that act in beneficial but undefined ways (154)(155)(156).…”

NRF2 promotes neuronal survival in neurodegeneration and acute nerve damage

“…They have long axons that project to distant targets, as do spinal cord motor neurons. A popular way to model nerve crush damage is to sever the optic nerve, and thus the RGC axons, whereupon the RGCs die within 2 weeks (36)(37)(38)(39). This then provides an excellent model of axonal injury.…”