Abstract
Neurons in the adult mammalian CNS fails to regenerate after severe injury. However, it is known that an increase in neural activity occurs in mouse retinal ganglion cells (RGCs) after extrinsic stimulation and this can induce axon growth. In the present study, we applied an optogenetic approach using a mouse model, specifically involving channelrhodopsin-2 (ChR2) expression in RGCs. We investigated whether modulation of RGC neural activity exclusively by blue light stimulation is able to promote neurite outgrowth of postnatal retinal explants. The results showed that activation of RGCs expressing ChR2 by 20 Hz blue light for 1 h is a most effective way of enhancing neurite outgrowth in postnatal retinas. This is achieved via gap junctions that spread neural activity across the whole retina. Moreover, we found that activation of intrinsic photosensitive RGCs (ipRGCs) by blue light also contributes significantly to the promotion of neurite outgrowth in the same postnatal retinal explants. Our findings not only demonstrate that a short-term increase in RGC neural activity is sufficient to facilitate the neurite outgrowth of retinal explants, but also highlight the fact that the temporal pattern of neural activity in RGCs is a critical factor in regulating axon regeneration.