1. Katome, T. et al. Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury. Cell Death Differ. 20, 270–280 (2013).
2. Noro, T. et al. Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury. Cell Death Dis. 6, e1720 (2015).
3. Benowitz, L. I., He, Z. & Goldberg, J. L. Reaching the brain: advances in optic nerve regeneration. Exp. Neurol. 287, 365–373 (2017).
4. Fujita, Y. & Yamashita, T. Axon growth inhibition by RhoA/ROCK in the central nervous system. Front. Neurosci. 8, 338 (2014).
5. Fournier, A. E., Takizawa, B. T. & Strittmatter, S. M. Rho kinase inhibition enhances axonal regeneration in the injured CNS. J. Neurosci. 23, 1416–1423 (2003).
6. Lingor, P. et al. Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo. J. Neurochem. 103, 181–189 (2007).
7. Ichikawa, M. et al. Differential effects of two ROCK inhibitors, Fasudil and Y-27632, on optic nerve regeneration in adult cats. Brain Res. 1201, 23–33 (2008).
8. Honjo, M. et al. Effects of rho-associated protein kinase inhibitor Y-27632 on intraocular pressure and outflow facility. Invest. Ophthalmol. Vis. Sci. 42, 137–144 (2001).
9. Tanihara, H. et al. Safety and efficacy of ripasudil in Japanese patients with glaucoma or ocular hypertension: 3-month interim analysis of ROCK-J, a post-marketing surveillance study. Adv. Ther. 36, 333–343 (2019).
10. Akaiwa, K. et al. Topical ripasudil suppresses retinal ganglion cell death in a mouse model of normal tension glaucoma. Invest. Ophthalmol. Vis. Sci. 59, 2080–2089 (2018).
11. Harada, T. et al. The potential role of glutamate transporters in the pathogenesis of normal tension glaucoma. J. Clin. Invest. 117, 1763–1770 (2007).
12. Harada, C., Kimura, A., Guo, X., Namekata, K. & Harada, T. Recent advances in genetically modified animal models of glaucoma and their roles in drug repositioning. Br. J. Ophthalmol. 103, 161–166 (2019).
13. Guo, X., Namekata, K., Kimura, A., Harada, C. & Harada, T. ASK1 in neurodegeneration. Adv. Biol. Regul. 66, 63–71 (2017).
14. Yamamoto, K. et al. The novel Rho kinase (ROCK) inhibitor K-115: a new candidate drug for neuroprotective treatment in glau- coma. Invest. Ophthalmol. Vis. Sci. 55, 7126–7136 (2014).
15. Namekata, K. et al. Dock3 stimulates axonal outgrowth via GSK-3β-mediated microtubule assembly. J. Neurosci. 32, 264–274 (2012).
16. Akiyama, G. et al. Edaravone prevents retinal degeneration in adult mice following optic nerve injury. Invest. Ophthalmol. Vis. Sci. 58, 4908–4914 (2017).
17. Liu, H. et al. Rho kinase inhibition by fasudil suppresses lipopolysaccharide-induced apoptosis of rat pulmonary microvascular endothelial cells via JNK and p38 MAPK pathway. Biomed. Pharmacother. 68, 267–275 (2014).
18. Zhou, H. et al. The RhoA/ROCK pathway mediates high glucose-induced cardiomyocyte apoptosis via oxidative stress, JNK, and p38MAPK pathways. Diabetes Metab. Res. Rev. 34, e3022 (2018).
19. Takamura, Y. et al. Vitreous and aqueous concentrations of brimonidine following topical application of brimonidine tartrate 0.1% ophthalmic solution in humans. J. Ocul. Pharmacol. Ther. 31, 282–285 (2015).
20. Semba, K. et al. Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma. Cell Death Dis. 5, e1341 (2014).
21. Fujita, Y., Sato, A. & Yamashita, T. Brimonidine promotes axon growth after optic nerve injury through Erk phosphorylation. Cell Death Dis. 4, e763 (2013).
22. Honda, et al. Survival of alpha and intrinsically photosensitive retinal ganglion cells in NMDA-induced neurotoxicity and a mouse model of normal tension glaucoma. Invest. Ophthalmol. Vis. Sci. 60, 3696–3707 (2019).
23. Duan, X. et al. Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signal- ing. Neuron 85, 1244–1256 (2015).
24. Li, S. et al. Promoting axon regeneration in the adult CNS by modulation of the melanopsin/GPCR signaling. Proc. Natl. Acad. Sci. USA 113, 1937–1942 (2016).
25. Fukata, Y. et al. CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nat. Cell Biol. 4, 583–591 (2002).
26. Mimura, F. et al. Myelin-associated glycoprotein inhibits microtubule assembly by a Rho-kinase-dependent mechanism. J. Biol. Chem. 281, 15970–15979 (2006).
27. Chiha, W., Bartlett, C. A., Petratos, S., Fitzgerald, M. & Harvey, A. R. Intravitreal application of AAV-BDNF or mutant AAV-CRMP2 protects retinal ganglion cells and stabilizes axons and myelin after partial optic nerve injury. Exp. Neurol. 326, 113167 (2020).
28. Namekata, K. et al. Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex. Proc. Natl. Acad. Sci. USA 107, 7586–7591 (2010).
29. Namekata, K., Kimura, A., Kawamura, K., Harada, C. & Harada, T. Dock GEFs and their therapeutic potential: neuroprotection and axon regeneration. Prog. Retin. Eye Res. 43, 1–16 (2014).
30. Blanquie, O. & Bradke, F. Cytoskeleton dynamics in axon regeneration. Curr. Opin. Neurobiol. 51, 60–69 (2018).
31. Leibinger, M. et al. GSK3-CRMP2 signaling mediates axonal regeneration induced by Pten knockout. Commun. Biol. 2, 318 (2019).
32. Noro, T. et al. Normal tension glaucoma-like degeneration of the visual system in aged marmosets. Sci. Rep. 9, 14852 (2019).
33. Namekata, K. et al. DOCK8 is expressed in microglia, and it regulates microglial activity during neurodegeneration in murine disease models. J. Biol. Chem. 294, 13421–13433 (2019).