Functional Recovery of Vision with Axonal Regeneration in Crushed Optic Nerve

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1.Axonal regeneration in crushed optic nerve with macrophage activationWhen oxidized galectin-1, a macrophage activator, was injected into the vitreous of adult cats, crushed axons of retinal ganglion cells (RGCs) extended beyond the crushed site. Regenerated axons continuously extended in the optic nerve (OpN) until 4 weeks, however no fibers newly entered into the OpN after 2 weeks.2.Promotion of neurite extension in retinal culture with ROCK inhibitors, Y-39983 and Y-27632We compared effects of Y-39983 (novel ROCK inhibitor) and Y-27632 on neurite extension in 3D retinal culture. Y-39983 promoted extension of both neurites and glial processes at 3-20 μM, totally inhibited the extension at 100 μM. Y-27632 promoted extension of only neurites at 10-30 μM, extension of both neurites and glial processes at 100-300 μM, totally inhibited the extension at 1 mM. Very few neurites emanated from retinal pieces in culture without the drugs.3.Axonal regeneration in crushed optic nerve with Y-39983 and Y-27632From the results in retinal culture, we adopted 10 μM Y-39983 to regenerate RGC axons into the crushed OpN. When Y-39983 was injected into the vitreous and crush site, many axons extended beyond the crush site in contrast with no fibers in saline injected OpN. The number of fibers were doubled in the OpN with second injection at day 7.4.OFF-RGCs have smaller ability to survive axotomy and regenerate axonsWhen RGCs regenerate axons into a transplanted peripheral nerve segment, number of ON-RGCs exceeds that on OFF-RGCs. An injection of BDNF, CNTF and forskolin increased only the number of OFF-RGCs regenerating axons as well as surviving axotomy. An injection of nipradilol, anti-glaucoma drug, increased number of OFF-RGCs surviving axotomy and regenerating axons.