[PDF] Effects of topical administration of y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys. | Semantic Scholar (2024)

Skip to search formSkip to main contentSkip to account menu

Semantic ScholarSemantic Scholar's Logo
@article{Tokushige2007EffectsOT, title={Effects of topical administration of y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys.}, author={Hideki Tokushige and Masaru Inatani and Shingo Nemoto and Hideyuki Sakaki and Koushirou Katayama and Masayoshi Uehata and Hidenobu Tanihara}, journal={Investigative ophthalmology \& visual science}, year={2007}, volume={48 7}, pages={ 3216-22 }, url={https://api.semanticscholar.org/CorpusID:9454042}}
  • H. Tokushige, M. Inatani, H. Tanihara
  • Published in Investigative Ophthalmology… 1 July 2007
  • Medicine

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.

171 Citations

Highly Influential Citations

5

Background Citations

48

Results Citations

3

Figures and Tables from this paper

  • figure 1
  • table 1
  • figure 2
  • table 2
  • figure 3
  • figure 4
  • figure 5
  • figure 6

171 Citations

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
    H. TokushigeM. WakiY. TakayamaH. Tanihara

    Medicine

    Current eye research

  • 2011

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
Effects of K-115, a Rho-Kinase Inhibitor, on Aqueous Humor Dynamics in Rabbits
    Tomoyuki IsobeK. MizunoYoshio KanekoMasayuki OhtaT. KoideS. Tanabe

    Medicine

    Current eye research

  • 2014

Results indicated that K-115 ophthalmic solution, a selective and potent ROCK inhibitor, is a novel and potent antiglaucoma agent.

Decreased intraocular pressure in mice following either pharmacological or genetic inhibition of ROCK.
    N. WhitlockB. Harrison D. Rice

    Biology, Medicine

    Journal of ocular pharmacology and therapeutics…

  • 2009

The magnitude of IOP reduction is significant as demonstrated with comparative pharmacology using agents that lower IOP in humans, and support the ROCK pathway as a therapeutic target for treating ocular hypertension.

  • 41
Effects of Rho-associated protein kinase inhibitors Y-27632 and Y-39983 on isolated rabbit ciliary arteries
    Hiroshi WatabeSanae AbeT. Yosh*tomi

    Medicine

    Japanese Journal of Ophthalmology

  • 2011

It is concluded that Y-27632 and Y-39983 relaxed isolated rabbit ciliary artery segments in vitro, and the mechanism of relaxation was not dependent on endothelial-derived factors such as nitric oxide (NO) or prostacyclin, nor was it dependent on changes in intracellular Ca2+ concentration.

  • 36
AMA0076, a novel, locally acting Rho kinase inhibitor, potently lowers intraocular pressure in New Zealand white rabbits with minimal hyperemia.
    S. Van de VeldeT. Van Bergen I. Stalmans

    Medicine

  • 2014

AMA0076 is a locally acting ROCK inhibitor that is able to induce altered cellular behavior of HTM cells that effectively reduces IOP in ocular normotensive and acute hypertensive rabbits without causing distinct hyperemia.

  • 82
  • PDF
The Effect of the H-1152P, a Potent Rho-Associated Coiled Coil-Formed Protein Kinase Inhibitor, in Rabbit Normal and Ocular Hypertensive Eyes
    M. NishioT. f*ckunaga Y. Uji

    Medicine

    Current eye research

  • 2009

Topical administration of H-1152P potently decreased rabbit normotensive IOPs in a dose-dependent manner, and the duration of the IOP lowering was also elongated in a doses dependent manner, suggesting that H- 1152P could be a candidate for the next generation of glaucoma therapy.

  • 39
A Highly Selective Rho-Kinase Inhibitor (ITRI-E-212) Potentially Treats Glaucoma Upon Topical Administration With Low Incidence of Ocular Hyperemia.
    Cherng-Ru HsuYi-Hsun Chen D. Lu

    Medicine

  • 2019

I-E-212 is a novel and highly specific ROCK2 inhibitor with the ability to lower IOP in animal models and has favorable pharmaco*kinetic and ocular tolerability profiles with only minimal conjunctival hyperemia.

  • 14
  • PDF
Potential role of Rho-associated protein kinase inhibitor Y-27632 in glaucoma filtration surgery.
    M. HonjoH. TaniharaT. KamedaT. KawajiN. YoshimuraM. Araie

    Medicine

  • 2007

Y-27632 had profound effects on activities of HTFs and was effective in preventing fibroproliferation and scar formation in a rabbit model of glaucoma surgery and a ROCK inhibitor may be an effective anti-scarring agent after glAUcoma filtering surgery.

  • 128
  • PDF
The effect of Rho-associated protein kinase inhibitor on monkey Schlemm's canal endothelial cells.
    T. KamedaToshihiro Inoue H. Tanihara

    Medicine

  • 2012

Y-27632 increased the permeability of the SCE-cell monolayer in association with disruption of the tight junction, F-actin depolymerization, and changes in various cell functions, including calcium transfer.

  • 93
  • PDF
The effect of Rho-associated kinase inhibition on the ocular penetration of timolol maleate.
    John J. ArnoldMark S. Hansen P. Challa

    Medicine

  • 2013

It is anticipated that care in order and timing of ROCK inhibitor administration will be warranted for those patients who may be on a multiple topical drug regimen for primary open-angle glaucoma.

  • 26
  • PDF

...

...

42 References

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
  • Highly Influential
Effects of protein kinase inhibitor, HA1077, on intraocular pressure and outflow facility in rabbit eyes.
    Megumi HonjoM. Inatani H. Tanihara

    Medicine

    Archives of ophthalmology

  • 2001

The results of in vitro experiments suggest that the IOP-lowering effects of HA1077 may be related to the altered cellular behavior of TM cells and relaxation of CM contraction, and have the potential to be developed into a treatment modality for glaucoma.

  • 115
  • 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
Effects of topical H-7 on outflow facility, intraocular pressure, and corneal thickness in monkeys.
    B. TianRong-Fang WangS. PodosP. Kaufman

    Medicine

    Archives of ophthalmology

  • 2004

Five percent H-7 increases outflow facility and decreases IOP, but does not affect corneal thickness, in monkeys with laser-induced unilateral glaucoma and multiple doses induce greater reduction of IOP than a single dose.

  • 23
  • PDF
Effects of ML-7 and Y-27632 on carbachol- and endothelin-1-induced contraction of bovine trabecular meshwork.
    R. RosenthalL. Choritz H. Thieme

    Medicine

    Experimental eye research

  • 2005
  • 68
H-7 disrupts the actin cytoskeleton and increases outflow facility.
    B. TianP. KaufmanT. VolbergB. GabeltB. Geiger

    Biology, Medicine

    Archives of ophthalmology

  • 1998

H-7 increases outflow facility in monkeys, probably by inhibiting cell contractility, cytoskeletal support, and cell-cell adhesions in the trabecular meshwork.

  • 131
  • PDF
Ocular hypotensive mechanism of topical isopropyl unoprostone, a novel prostaglandin metabolite-related drug, in rabbits.
    Toru TaniguchiM. S. R. HaqueKazuhisa SugiyamaNobuhide HoriYoshiaki Kitazawa

    Medicine

    Journal of ocular pharmacology and therapeutics…

  • 1996

Unoprostone lowers the IOP by affecting aqueous outflow pathways, primarily the pressure-dependent conventional pathway and the secondary uveoscleral outflow pathway in rabbits.

  • 80
Involvement of Rho p21 small GTP-binding protein and its regulator in the HGF-induced cell motility.
    K. TakaishiTakuya Sasaki Y. Takai

    Biology, Medicine

    Oncogene

  • 1994

Results indicate that both rho p21 and rho GDI, but neither rac p21 nor ras p21, are involved in the HGF-induced cell motility.

  • 205
Role of lysophospholipid growth factors in the modulation of aqueous humor outflow facility.
    Priyatham S. MettuPeifeng DengU. K. MisraG. GawdiD. EpsteinP. Rao

    Biology, Medicine

  • 2004

These studies demonstrate that LPA and S1P, the physiological agonists of Edg receptors, decrease outflow facility in perfused porcine eyes in association with increased MLC phosphorylation and Rho guanosine triphosphatase (GTPase) activation.

  • 95
  • PDF

...

...

Related Papers

Showing 1 through 3 of 0 Related Papers

    [PDF] Effects of topical administration of y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys. | Semantic Scholar (2024)

    FAQs

    What are the effects of rho-associated protein kinase inhibitor Y-27632 on intraocular pressure and outflow facility? ›

    conclusions. Administration of Y-27632 caused a reduction in IOP and an increase in the outflow facility.

    What is the mechanism of action of Y-27632? ›

    Y-27632 is an inhibitor of Rho-associated protein kinase. It inhibits calcium sensitization to affect smooth muscle relaxation.

    What are the side effects of rho kinase inhibitors? ›

    It has also been clinically approved to treat glaucoma, specifically in the United States, and its intraocular pressure lowering effect has been shown to increase with latanoprost. Side effects of Netarsudil include conjunctival hyperemia and corneal verticillata, instillation site pain, and conjunctival hemorrhages.

    What are the side effects of protein kinase inhibitors? ›

    However, KIs have important side effects, including fatigue, hypertension, rash, impaired wound healing, myelosuppression, and diarrhea (14). The overall toxicity of KIs, although less life-threatening than conventional cytotoxic chemotherapy, nevertheless is common and may require dose reduction.

    What does ROCK inhibitor do to stem cells? ›

    ROCK inhibition enables maintenance of stem cell phenotype; its effects on metabolism are unknown. hPSCs were exposed to 10 μM ROCK inhibitor for varying exposure times. Pluripotency (TRA-1-81, SSEA3, OCT4, NANOG, SOX2) remained unaffected, until after prolonged exposure (96 hrs).

    What is the working concentration of ROCK inhibitor Y-27632? ›

    For most hESC applications, reconstitute Y-27632 (Molar mass: 338.3) to 1 mM stock concentration in sterile distilled water. Aliquot and store at -20°C for up to one year. Aliquots can be thawed and diluted to a working concentration of 10 μM for hESC applications.

    What is the mechanism of action of RTK inhibitors? ›

    Tyrosine kinase inhibitors are small molecules that compete with the adenosine triphosphate-binding site of the catalytic domain of a tyrosine kinase. Occupation of this site inhibits autophosphorylation and activation of the tyrosine kinase, and prevents further activation of intracellular signaling pathways.

    How do rho kinase inhibitors reduce IOP? ›

    Current ROCK Inhibitors

    It is a novel ocular hypotensive agent used in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). It lowers IOP primarily by increasing outflow through TM in addition to decreasing both AH production and episcleral venous pressure.

    What is the function of the rho associated protein kinase? ›

    Rho kinases (Rho associated protein kinase, ROCK) are serine or threonine kinases that determine the calcium sensitivity in smooth muscle cells (see Fig. 8.9) and contribute to the regulation of a variety of functions including smooth muscle contraction, gene expression, proliferation, and apoptosis.

    What is the mechanism of action of rho kinase inhibitors? ›

    Rho kinase inhibitors help lower IOP by increasing AH outflow, reducing AH production, and decreasing episcleral venous pressure (EVP) [36]. This is done in two different ways, which involves Rho kinase pathway inhibition and, as with Netarsudil, norepinephrine transport inhibition.

    What does Rho-kinase do in glaucoma? ›

    Rho kinase (ROCK) inhibitors are a new class of glaucoma drugs with a novel mechanism of action and good safety profile. They exert neuroprotective effects, act on the trabecular tissue, increase the outflow of aqueous humor, and reduce intraocular pressure.

    Top Articles
    Latest Posts
    Article information

    Author: Manual Maggio

    Last Updated:

    Views: 6134

    Rating: 4.9 / 5 (69 voted)

    Reviews: 92% of readers found this page helpful

    Author information

    Name: Manual Maggio

    Birthday: 1998-01-20

    Address: 359 Kelvin Stream, Lake Eldonview, MT 33517-1242

    Phone: +577037762465

    Job: Product Hospitality Supervisor

    Hobby: Gardening, Web surfing, Video gaming, Amateur radio, Flag Football, Reading, Table tennis

    Introduction: My name is Manual Maggio, I am a thankful, tender, adventurous, delightful, fantastic, proud, graceful person who loves writing and wants to share my knowledge and understanding with you.