title: A novel ROCK inhibitor, Y-39983, promotes regeneration of crushed axons of retinal ganglion cells into the optic nerve of adult cats.
abstract: We investigated the effect of a novel ROCK inhibitor, Y-39983, on neurite regeneration in vitro and axonal regeneration in the crushed cat optic nerve in vivo. To determine the effective dose for neurite regeneration, retinal pieces were cultured with ROCK inhibitors, Y-39983 or Y-27632, a well-characterized ROCK inhibitor, and the number and length of TUJ-1-positive neurites were evaluated. The greatest number of neurites protruded at a dose of 3-10 microM Y-39983 and at a dose of 10-100 microM Y-27632, respectively. The neurite number at maximum effect of Y-39983 was greater than that of Y-27632. No significant difference was observed between values of neurite length with the inhibitors. Based on this finding, we examined the effect of Y-39983 on axonal regeneration in the crushed optic nerve in vivo. Immediately after crushing the left optic nerve, Y-39983 was injected into the vitreous and the crushed site. An injection of 10 microM Y-39983 induced the crushed axons to regenerate and pass over the crush site. In contrast, very few axons passed beyond the crush site in the optic nerve with phosphate-buffered saline injection. The second injection of 10 microM Y-39983 on day 7 doubled the number of regenerated axons, suggesting that new axons may have entered into the optic nerve after day 7 and that a continuous supply of the drug may make more axons to regenerate.
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Tsuruma-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Sagawa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Terasaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ichikawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yata
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Tokita
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects*; D002415:Cats; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007267:Injections; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D008297:Male; D009409:Nerve Crush; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects*; D009457:Neuroglia / Q000187:drug effects; D009900:Optic Nerve / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D013997:Time Factors; D014822:Vitreous Body; D054460:rho-Associated Kinases
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C520365:Y-39983; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases