Topical ripasudil stimulates neuroprotection and axon regeneration in adult mice following optic nerve injury

Euido Nishijima,Atsuko Kimura,Tadashi Nakano,Kazuhiko Namekata,Takayuki Harada,Xiaoli Guo,Chikako Harada,Takahiko Noro

doi:10.1038/s41598-020-72748-3

Euido Nishijima, Atsuko Kimura + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-72748-3

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Abstract

Optic nerve injury induces optic nerve degeneration and retinal ganglion cell (RGC) death that lead to visual disturbance. In this study, we examined if topical ripasudil has therapeutic potential in adult mice after optic nerve crush (ONC). Topical ripasudil suppressed ONC-induced phosphorylation of p38 mitogen-activated protein kinase and ameliorated RGC death. In addition, topical ripasudil significantly suppressed the phosphorylation of collapsin response mediator protein 2 and cofilin, and promoted optic nerve regeneration. These results suggest that topical ripasudil promotes RGC protection and optic nerve regeneration by modulating multiple signaling pathways associated with neural cell death, microtubule assembly and actin polymerization.

Highlights

Optic nerve injury induces optic nerve degeneration and retinal ganglion cell (RGC) death that lead to visual disturbance
We previously reported that topical ripasudil prevents glaucomatous retinal degeneration[10] in excitatory amino acid carrier 1 (EAAC1) knockout (KO) mice, a mouse model of normal tension glaucoma (NTG)[11,12]
We examined the effects of topical ripasudil on RGC protection and axon regeneration using an optic nerve crush (ONC) model

Summary

Introduction

Optic nerve injury induces optic nerve degeneration and retinal ganglion cell (RGC) death that lead to visual disturbance. Topical ripasudil significantly suppressed the phosphorylation of collapsin response mediator protein 2 and cofilin, and promoted optic nerve regeneration. These results suggest that topical ripasudil promotes RGC protection and optic nerve regeneration by modulating multiple signaling pathways associated with neural cell death, microtubule assembly and actin polymerization. Ripasudil strongly suppressed oxidative stress-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) that stimulates RGC death in EAAC1 KO m ice[10,13]. These results suggest that ripasudil promotes RGC protection by stimulating both IOP-dependent and IOP-independent pathways. We examined the effects of topical ripasudil on RGC protection and axon regeneration using an ONC model

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