Abstract
Mature mammalian central nervous system fails to regenerate after severe injuries. However, it is known that gradual loss of axon growth ability of retinal ganglion cells (RGCs) during development is largely determined by extrinsic signals rather than programmed genetically. Spontaneous retinal waves are the major neural activity during retinal development. Thus, restoring developmental environment by mimicking these neural activities may provide help to axon regeneration of RGCs. Here we demonstrated that neurite outgrowth of retinal explants was greatly enhanced when short term electrical stimulation similar to stage II retinal waves was applied to the retinas normally displayed stage III retinal waves. Similarly, short term induction of globally wave-like neural activity by blocking inhibitory neural transmission in the same age of retinas also greatly promoted neurite outgrowth even in the absence of exogenous neurotrophic factors. Surprisingly, neurite outgrowth was significantly reduced when glutamate transmission was blocked pharmacologically in the retinas normally displayed stage II cholinergic retinal waves. These findings support that short term restoration of environments that mimic neural activities of developmentally precedent retinas is sufficient to enhance neurite outgrowth of retinal explants, and may lead to a therapeutic strategy of preventing the gradual loss of axon growth ability of RGCs in more mature retinas. Key words: retinal waves, retinal ganglion cells, electrical stimulation, axon regeneration, neurotrophic factors