Effects of Y-39983, a Selective Rho-Associated Protein Kinase Inhibitor, on Blood Flow in Optic Nerve Head in Rabbits and Axonal Regeneration of Retinal Ganglion Cells in Rats | Semantic Scholar (2024)

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@article{Tokushige2011EffectsOY, title={Effects of Y-39983, a Selective Rho-Associated Protein Kinase Inhibitor, on Blood Flow in Optic Nerve Head in Rabbits and Axonal Regeneration of Retinal Ganglion Cells in Rats}, author={Hideki Tokushige and Mitsunori Waki and Yoshiko Takayama and Hidenobu Tanihara}, journal={Current Eye Research}, year={2011}, volume={36}, pages={964 - 970}, url={https://api.semanticscholar.org/CorpusID:481367}}
  • H. Tokushige, M. Waki, H. Tanihara
  • Published in Current Eye Research 27 September 2011
  • Medicine

Y-39983 may be a candidate drug not only for lowering of IOP but also for increasing of blood flow in ONH in the treatment of glaucoma, although improvements of formulation or route of administration are needed in order to reach an effective concentration in retina.

62 Citations

Background Citations

18

Results Citations

3

62 Citations

Y-39983 downregulates RhoA/Rho-associated kinase expression during its promotion of axonal regeneration.
    Zijian YangJing WangXiao-hong LiuY. ChengL. DengY. Zhong

    Biology, Medicine

    Oncology reports

  • 2013

It is demonstrated that Y-39983 significantly enhanced the survival and axonal regeneration of RGCs after ONC and downregulated the expression of active-RhoA, ROCK1 and ROCK2 during its promotion of axonal Regeneration.

  • 21
  • PDF
Topical administration of a Rock/Net inhibitor promotes retinal ganglion cell survival and axon regeneration after optic nerve injury
    P. ShawAlan Sang J. Goldberg

    Medicine

    Experimental eye research

  • 2017
Fasudil, a Rho-Associated Protein Kinase Inhibitor, Attenuates Traumatic Retinal Nerve Injury in Rabbits
    Jianglong YuXinping LuanShiying LanBaofeng YanA. Maier

    Medicine

    Journal of Molecular Neuroscience

  • 2015

Fasudil treatment could significantly reduce the apoptosis of RGCs and relieved retinal nerve injury in vitro and in vivo, and showed that RhoA/Rock signaling in the retina was activated during the traumatic optic neuropathy.

  • 13
Regeneration of optic nerve fibers with unoprostone, a prostaglandin-related antiglaucoma drug, in adult cats
    H. SagawaH. TerasakiKeiko NakanishiYoshihito TokitaMasami Watanabe

    Medicine, Biology

    Japanese Journal of Ophthalmology

  • 2013

The results indicate that intravitreal injection of unoprostone promotes regeneration of crushed optic nerve fibers in adult cats.

The novel Rho kinase (ROCK) inhibitor K-115: a new candidate drug for neuroprotective treatment in glaucoma.
    Kotaro YamamotoK. Maruyama T. Nakazawa

    Medicine

  • 2014

The findings show that K-115 has a potential use in neuroprotective treatment for glaucoma and other neurodegenerative diseases and that it did not suppress ROS production directly.

  • 129
  • PDF
Effect of the Rho Kinase Inhibitor Y-27632 on Corneal Endothelial Wound Healing.
    Naoki OkumuraRyota Inoue N. Koizumi

    Medicine

  • 2015

Preliminary human cases confirmed that ROCK inhibitor eye drops were considerably effective for treatment of corneal edema associated with cataract surgery, and ROCK inhibitor may be developed as an eye drop for treating acuteCorneal endothelial damage to prevent progression of bullous keratopathy.

  • 76
  • PDF
Effects of ripasudil, a rho kinase inhibitor, on blood flow in the optic nerve head of normal rats
    Yasushi WadaT. HigashideA. NagataK. Sugiyama

    Medicine

    Graefe's Archive for Clinical and Experimental…

  • 2018

Topical instillation of ripasudil increased blood flow around the ONH in the eyes of normal rats, and mean blur rate was evaluated in the total area, the vessel region, and the tissue region.

  • 9
The Neuroprotective Potential of Rho-Kinase Inhibition in Promoting Cell Survival and Reducing Reactive Gliosis in Response to Hypoxia in Isolated Bovine Retina
    A. AltR. Hilgers M. Lüke

    Biology, Medicine

    Cellular Physiology and Biochemistry

  • 2013

H-1152P exerted a neuroprotective effect against necrosis on the isolated bovine retina under Hypoxia together with a reduction in glial cell reactivity, however, the inhibitor could not prevent the hypoxia induced retinal dysfunction possibly due to the interference with synaptic modulation.

  • 13
  • PDF
Effect of intravitreal Rho kinase inhibitor ripasudil (K-115) on feline retinal microcirculation.
    Seigo NakabayashiMotofumi Kawai T. Nagaoka

    Biology, Medicine

    Experimental eye research

  • 2015
  • 13
Effects of Rho Kinase Inhibitors on Intraocular Pressure and Aqueous Humor Dynamics in Nonhuman Primates and Rabbits.
    C. TorisM. Mclaughlin G. Prasanna

    Medicine

    Journal of ocular pharmacology and therapeutics…

  • 2016

The Y-27632 effect on IOP in hypertensive NHP eyes is caused by increases in outflow facility and uveoscleral outflow, and an increase in aqueous humor formation attenuates but does not prevent an IOP decrease.

  • 20

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42 References

Effects of topical administration of y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys.
    H. TokushigeM. Inatani H. Tanihara

    Medicine

  • 2007

Y-39983 ophthalmic solution may be a candidate drug for lowering of intraocular pressure (IOP), since it increases conventional outflow and produces relatively few side effects.

  • 172
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A novel ROCK inhibitor, Y-39983, promotes regeneration of crushed axons of retinal ganglion cells into the optic nerve of adult cats
    H. SagawaH. Terasaki M. Watanabe

    Biology, Medicine

    Experimental Neurology

  • 2007
  • 67
Effects of fasudil, a Rho-associated protein kinase inhibitor, on optic nerve head blood flow in rabbits.
    T. SugiyamaMaho Shibata T. Ikeda

    Medicine

  • 2011

Results show that systemic or topical fasudil suppresses impairment of ONH blood flow, function, and morphology induced by L-NAME or ET-1, and a ROCK inhibitor can be useful for the treatment of impaired ONHBlood flow.

  • 68
  • PDF
Effects of rho-associated protein kinase inhibitor Y-27632 on intraocular pressure and outflow facility.
    M. HonjoH. Tanihara Yoshihito Honda

    Medicine

  • 2001

In vitro experiments suggest that the IOP-lowering effects of Y-27632 may be related to the altered cellular behavior of TM cells and relaxation of CM contraction, and suggest that ROCK inhibitors may have great potential to be developed for treatment of glaucoma and other ocular diseases.

  • 380
Efficacy of Rho-kinase inhibition in promoting cell survival and reducing reactive gliosis in the rodent retina.
    A. TuraF. SchuettaufP. MonnierK. Bartz-SchmidtS. Henke-Fahle

    Medicine, Biology

  • 2009

The results demonstrate the neuroprotective effect of H-1152P-mediated ROCK-inhibition on retinal cells under stress, which may rely partly on the attenuation of glial cell reactivity.

  • 79
  • PDF
Neurotoxic effects of low doses of glutamate on purified rat retinal ganglion cells.
    Y. OtoriJi-ye WeiC. Barnstable

    Biology, Medicine

  • 1998

This is the first report to show the functional role of calcium-permeable AMPA-KA receptors in cultured RGCs, which causes increases in intracellular calcium and decreases in cell survival.

  • 161
  • PDF
Reduction of intraocular pressure by topical administration of an inhibitor of the Rho-associated protein kinase
    M. WakiY. YoshidaT. OkaM. Azuma

    Medicine

    Current eye research

  • 2001

The ROCK inhibitor reduced intraocular pressure in rabbits by topical instillation and relaxed the excised ciliary muscle which was previously constricted by carbachol suggesting that the inhibitor acts to increase the uveoscleral outflow.

  • 100
Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y-27632.
    P. RaoPeifeng DengJ. KumarD. Epstein

    Medicine

  • 2001

PURPOSEThe goal of this study was to investigate the role of Rho kinase in the modulation of aqueous humor outflow facility. Rho kinase, a critical downstream effector of Rho GTPase is recognized to

  • 420
Molecular Dissection of the Rho-associated Protein Kinase (p160ROCK)-regulated Neurite Remodeling in Neuroblastoma N1E-115 Cells
    Masaya HiroseT. Ishizaki S. Narumiya

    Biology

    The Journal of cell biology

  • 1998

It is shown that p160ROCK activation is necessary and sufficient for the agonist-induced neurite retraction and cell rounding, and Rho/ROCK-dependent tonic inhibition of cell process extension is exerted via activation of the actomysin-based contractility, in conjunction with a suppression of assembly of intermediate filaments and microtubules in many cell types including, but not exclusive to, neuronal cells.

  • 481
  • PDF
Time course of changes in optic nerve head circulation after acute reduction in intraocular pressure.
    J. TakayamaA. TomidokoroY. TamakiM. Araie

    Medicine

  • 2005

The findings suggest the importance of vascular smooth muscle in maintaining stable ONH circulation against reduction of IOP in a fashion nearly independent of NO, endogenous prostaglandins, and the sympathetic nervous system.

  • 17
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    Effects of Y-39983, a Selective Rho-Associated Protein Kinase Inhibitor, on Blood Flow in Optic Nerve Head in Rabbits and Axonal Regeneration of Retinal Ganglion Cells in Rats | Semantic Scholar (2024)
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