視神経再生療法の未来

The optic nerve is a part of the central nervous system （CNS） and convey visual signals from the retina along their axons to the brain. Axonal damage can be induced by trauma, ischemia or in glaucoma, the most common cause of blindness in Japan. Like other CNS axons, the optic nerve has a very limited regenerative capacity. However, recent advances in research have revealed that combinational treatments, for example, overcoming the inhibitory environment of the glial scar and activating the intrinsic growth program, yield robust optic nerve regeneration. In addition, we revealed that overexpression of dedicator of cytokinesis 3 （Dock3）, one of the atypical Rho-guanine nucleotide exchange factors （Rho-GEFs）, plays important roles in promoting optic nerve regeneration. In response to the brain-derived neurotrophic factor （BDNF）, Dock3 activates multiple pathways that stimulate both actin polymerization and microtubule assembly, which are processes involved in neuroregeneration. Furthermore, Dock3 prevents glaucomatous retinal degeneration by suppressing both glutamate neurotoxicity and oxidative stress, suggesting that Dock3 signaling is a potential therapeutic target for both optic nerve regeneration and retinal neuroprotection. Based on our current knowledge, a combinatory approach including stimulation of Dock3 signalling may be effective for the treatment of complex diseases such as glaucoma, and this type of strategy may be available for future regeneration therapy using induced pluripotent stem （iPS） cells.