TY - JOUR T1 - Blue light promotes neurite outgrowth of retinal explants in postnatal ChR2 mice JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0391-18.2019 SP - ENEURO.0391-18.2019 AU - Chin-I Lin AU - Chuan-Chin Chiao Y1 - 2019/07/30 UR - http://www.eneuro.org/content/early/2019/07/29/ENEURO.0391-18.2019.abstract N2 - 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 one hour 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 intrinsically photosensitive retinal ganglion cells 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.Significance Statement Neurons in the mammalian central nervous system rarely regenerate and typically die soon after injury. The use of optogenetics in promoting axon regrowth has been recognized in recent years. However, the potential of optogenetics has not been fully explored in treating optic nerve injury and glaucoma. By using the mice with channelrhodopsin-2 expressed specifically in retinal ganglion cells (RGCs) and stimulating the retinal explants with blue light, this project reveals that the temporal pattern of neural activity in RGCs is an important factor driving neurite outgrowth. In addition, intrinsic photosensitive RGCs also contribute in facilitating axon growth in postnatal animals. This study thus provides significant insights into the development of therapeutic strategy for axon regeneration of RGCs. ER -