Rho kinase inhibitors for glaucoma treatment - Review

Germano, Renato Antunes Schiave; Finzi, Simone; Challa, Pratap; Susanna, Remo

doi:10.5935/0004-2749.20150103

Cited by 7 publications

(9 citation statements)

References 44 publications

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“…The fibrogenic effect caused by TGFβ2 is believed to be mediated, in part, by activated RhoGTPase/Rho-associated kinase (ROCK). ROCK-inhibitors are a novel potential class of glaucoma therapeutics offering distinct applications including reduced IOP, improved ocular blood flow, inhibition of postoperative scarring, and even neuroprotection910. With demonstrated effectiveness in animal models, several ROCK-inhibitors are currently undergoing Phase II and III clinical trials in glaucoma1011.…”

mentioning

confidence: 99%

“…With demonstrated effectiveness in animal models, several ROCK-inhibitors are currently undergoing Phase II and III clinical trials in glaucoma1011. ROCK inhibitors can affect the contractile properties of HTM cells, α-smooth muscle actin (α-SMA) expression, ECM accumulation in the outflow pathway and aqueous humor outflow9101112. Several of these factors are also affected by TGFβ2, suggesting a common pathway.…”

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confidence: 99%

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TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor

Torrejon

Papke

Halman

et al. 2016

Sci Rep

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Members of the transforming growth factor beta (TGFβ) cytokine family have long been associated with affecting several cellular functions, including cell proliferation, differentiation and extracellular matrix (ECM) turnover. Of particular interest to this work, TGFβ2 has been linked to most types of glaucomas as a potential fibrotic agent that can cause elevation of intraocular pressure (IOP). Given that the trabecular meshwork (TM) provides most of aqueous humor outflow resistance in the eye, an in vitro bioengineered human TM (HTM) model has been created and validated by analyzing effects of TGFβ2 on transcellular pressure changes and outflow facility. These changes were correlated with several biological alterations induced by this cytokine, including ECM production and overexpression of HTM-marker myocillin. Furthermore, this TM model has been used to extend current knowledge of gene expression of cytokines involved in TGFβ-induced ECM turnover over time. In particular, the ability for a ROCK-inhibitor to diminish the effect of TGFβ on TM was demonstrated. This work supports the notion that anti-fibrotic activities of ROCK-inhibitors could counteract the elevation of IOP and increased strain observed in glaucomatous TM.

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confidence: 99%

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confidence: 99%

TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor

Torrejon

Papke

Halman

et al. 2016

Sci Rep

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“…Rao (2001) stated that the Y-27632 increased permeability and changes in cell adhesion as well as relaxation of the trabecular meshwork. Germano (2015) identified that the precise mechanism of Rho-kinase inhibitor in increasing the conventional outflow of aqueous humor is not utterly understood. It was assumed that the cytoskeleton system is disturbed by the inhibition of rho-kinase activity.…”

Section: Resultsmentioning

confidence: 99%

“…Trabecular meshwork tissue is considered to obtain regulatory mechanism as it also has smooth-muscle-like properties. The actomyosin system has contributed to the regulation of contraction as well as relaxation of the tissue [8].…”

Section: Resultsmentioning

confidence: 99%

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Rho- Kinase Inhibitor Y-27632 Decreases the Thickness of Trabecular Meshwork in Juvenile Rats Mod-el Injected with Sodium Hyaluronate

Vierlia

Wulandari²,

Sujuti³

et al. 2018

J.Trop.Life.Science

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Most glaucoma drugs lower the intraocular pressure (IOP) by decreasing the aqueous humor production and increasing the outflow through uveoscleral pathway. None of these drugs work mainly on increasing outflow through the trabecular pathway. Consequently, the experiment to develop glaucoma drugs directly target at the trabecular outflow pathway is highly required. The purpose of this study is to reveal the effect of rho-kinase inhibitor Y-27632 on the thickness of trabecular meshwork in juvenile rats model injected with sodium hyaluronate. This study was an experimental study with posttest only control group design. Twenty-four rats were included in this study. Each eye of the rat would be considered as one sample. Samples were divided into 6 groups, negative control group, positive control I group with intracameral sodium hyaluronate injection, positive control II group with topical Y-27632 10 mM, and three experimental groups with intracameral injection of sodium hyaluronate and Y-27632 10-1 mM, 1 mM, and 10 mM respectively. After the procedures all rats were sacrificed and enucleated. Trabecular meshwork tissue was stained with Hematoxilene-Eosin and evaluated under 400× microscopic magnification. Quantitative measurements were taken using computerized image analysis with dot slide program. There were significant statistic differences among the positive control I group and the experimental groups (p-value < 0.05) as well as the positive control II group and the experimental groups (p-value < 0.05). The highest mean of decreasing trabecular meshwork thickness was noted in the group given by sodium hyaluronate and Y-27632 10 mM with value of 118.42 µm. There was decreasing thickness of trabecular meshwork due to the effect of rho-kinase inhibitor Y-27632 in juvenile rats injected with sodium hyaluronate.

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Rho kinase inhibitors—a review on the physiology and clinical use in Ophthalmology

Moura-Coelho

Ferreira

Bruxelas

et al. 2019

Graefes Arch Clin Exp Ophthalmol

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Rho kinase inhibitors for glaucoma treatment - Review

Cited by 7 publications

References 44 publications

TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor

TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor

Rho- Kinase Inhibitor Y-27632 Decreases the Thickness of Trabecular Meshwork in Juvenile Rats Mod-el Injected with Sodium Hyaluronate

Rho kinase inhibitors—a review on the physiology and clinical use in Ophthalmology

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