Effect of Rho Kinase Inhibitor on the Production of Nitric Oxide in Trabecular Meshwork Cells

Kim, Jae Woo; Kim, Keun Hae; Hwang, Seok Jin

doi:10.3341/jkos.2016.57.4.650

Cited by 2 publications

(1 citation statement)

References 23 publications

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“…32 In animal and human models, ROCK inhibitors have been shown to increase trabecular outflow facility and lower IOP. [32][33][34][35] Earlier animal studies even demonstrated a potential neuroprotective effect by improving blood flow to the optic nerve after topical application in rabbit eyes. 3 Netarsudil (formerly AR 13324) is the first ROCK inhibitor to become available clinically for glaucoma.…”

Section: Netarsudil (Rhopressa)mentioning

confidence: 99%

New considerations for the clinical efficacy of old and new topical glaucoma medications

MacIver

Stout²,

Ricci

2021

Clinical and Experimental Optometry

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Glaucoma is the most common form of irreversible blindness in the world. Lowering intraocular pressure (IOP) remains the only clinically established method of treatment to slow the progression of glaucoma. Primary open angle glaucoma is a disease of the optic nerve head and often is associated with changes to the trabecular meshwork that cause a reduction to aqueous humour outflow and an increase in intraocular pressure. Until recently, topical IOP lowering medication has been limited to the mechanisms of action of decreasing aqueous production and/or redirecting outflow to the unconventional uveoscleral outflow pathway. Both of these mechanisms neglect to treat or act on tissue that becomes altered from glaucoma. Latanoprostene-bunod 0.024%, a nitric-oxide donating prostanoid, netarsudil 0.02%, a potent Rho-associated protein kinase (ROCK) inhibitor and norepinephrine transporter inhibitor, and a once daily dosed fixed combination medication with netarsudil 0.02% and latanoprost 0.005% have recently come on the market. This paper will discuss and review the limitations to traditional IOP lowering glaucoma medications as well as the mechanism of actions and clinical efficacy of the new glaucoma medications. It will also discuss how the new class of glaucoma medications might help to overcome some known limitations in treatment and barriers to patient adherence.

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Section: Netarsudil (Rhopressa)mentioning

confidence: 99%

New considerations for the clinical efficacy of old and new topical glaucoma medications

MacIver

Stout²,

Ricci

2021

Clinical and Experimental Optometry

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Effect of Low Concentration Rho-kinase inhibitor on the Permeability and Nitric Oxide Production in Trabecular Meshwork

김

2019

J Korean Glaucoma Soc

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이 연구되고 있으며 3 이러한 약제의 하나로 Rho-kinase (ROCK) 저해제가 있다. 4 ROCK 저해제는 섬유주를 이완시켜 방수 유출을 증가시키는 데, 주된 기전은 F-액틴의 중합을 저해하고 세포내 칼슘을 조절함 으로써 세포 간 밀착연접(tight junction)을 해체시켜 섬유주를 통 한 방수 유출을 증가시키는 것으로 알려져 있다. 5 ROCK 저해제 의 일종인 Y-27632는 여러 연구에서 방수 유출을 증가시키는 작 용을 나타내는 것으로 보고되어 있다. 6-9 자유유리기인 일산화질소(nitric oxide, NO)는 세포의 종류에 따라 다양한 역할을 나타낼 수 있으며, 평활근 이완 효과도 나타 내는 것으로 알려져 있다. 섬유주세포는 형태학적 연구와 전기생 리학적 연구에서 평활근과 유사한 성질을 가진 것으로 알려져 있 으며 10,11 endothelial nitric oxide synthase (eNOS)에서 생산하는 NO는 섬유주를 이완시켜 방수 유출을 촉진하는 것으로 알려져 있다. 12-14 ROCK 저해제의 작용기전은 섬유주 주변 세포의 형태학적 변 화와 액틴스트레스 섬유에 영향을 미쳐 섬유주를 이완시키고 쉴Purpose: To investigate the effects of the lower concentration of Rho-kinase (ROCK) inhibitor on the permeability of trabecular cell monolayer and its relationship with nitric oxide (NO) production in cultured human trabecular meshwork cells (HTMC). Methods: Primarily cultured HTMC were exposed to 0, 5, 10, 20 mM Y-27632 for 24 hours. NO production and expression of endothelial nitric oxide synthase (eNOS) mRNA were measured with Griess assay and Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The permeability of the HTMC monolayer was determined using Transwell and carboxyfluorescein. After inducing oxidative stress with 200 mM hydrogen peroxide, above experiments were done simultaneously. Results: In HTMC, 5, 10, and 20 mM Y-27632 significantly increased the permeability of the HTMC monolayer (all p < 0.05) in a dose-dependent manner. In contrast, 5, 10 mM Y-27632 did not increase NO production and expression of eNOS mRNA significantly (p > 0.05). Experiments under the oxidative stress showed similar results. Conclusion: ROCK inhibitor increased trabecular permeability in a dose-dependent manner but this increase was not accompanied with increased NO production. At low concentration, ROCK inhibitor-induced increased trabecular outflow may be not associated with NO production.

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Effect of Rho Kinase Inhibitor on the Production of Nitric Oxide in Trabecular Meshwork Cells

Cited by 2 publications

References 23 publications

New considerations for the clinical efficacy of old and new topical glaucoma medications

New considerations for the clinical efficacy of old and new topical glaucoma medications

Effect of Low Concentration Rho-kinase inhibitor on the Permeability and Nitric Oxide Production in Trabecular Meshwork

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