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Rho 激酶抑制剂在角膜疾病中的作用。

The Role of Rho Kinase Inhibitors in Corneal Diseases.

机构信息

Department of Ophthalmology, University Hospital of Basel, Basel, Switzerland.

Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.

出版信息

Drug Des Devel Ther. 2024 Jan 19;18:97-108. doi: 10.2147/DDDT.S435522. eCollection 2024.


DOI:10.2147/DDDT.S435522
PMID:38264539
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10804875/
Abstract

The cornea, as the outermost layer of the eye, plays a crucial role in vision by focusing light onto the retina. Various diseases and injuries can compromise its clarity, leading to impaired vision. This review aims to provide a thorough overview of the pharmacological properties, therapeutic potential and associated risks of Rho-associated protein kinase (ROCK) inhibitors in the management of corneal diseases. The article focuses on four key ROCK inhibitors: Y-27632, fasudil, ripasudil, and netarsudil, providing a comparative examination. Studies supporting the use of ROCK inhibitors highlight their efficacy across diverse corneal conditions. In Fuchs' endothelial corneal dystrophy, studies on the application of Y-27632, ripasudil, and netarsudil demonstrated noteworthy enhancements in corneal clarity, endothelial cell density, and visual acuity. In pseudophakic bullous keratopathy, the injection of Y-27632 together with cultured corneal endothelial cells into the anterior chamber lead to enhanced corneal endothelial cell density and improved visual acuity. Animal models simulating chemical injury to the cornea showed a reduction of neovascularization and epithelial defects after application of fasudil and in a case of iridocorneal endothelial syndrome netarsudil improved corneal edema. Addressing safety considerations, netarsudil and ripasudil, both clinically approved, exhibit adverse events such as conjunctival hyperemia, conjunctival hemorrhage, cornea verticillata, conjunctivitis, and blepharitis. Monitoring patients during treatment becomes crucial to balancing the potential therapeutic benefits with these associated risks. In conclusion, ROCK inhibitors, particularly netarsudil and ripasudil, offer promise in managing corneal diseases. The comparative analysis of their pharmacological properties and studies supporting their efficacy underscore their potential therapeutic significance. However, ongoing research is paramount to comprehensively understand their safety profiles and long-term outcomes in diverse corneal conditions, guiding their optimal application in clinical practice.

摘要

角膜作为眼睛的最外层,在将光线聚焦到视网膜上方面起着至关重要的作用。各种疾病和损伤都可能损害其透明度,导致视力受损。本综述旨在全面概述 Rho 相关蛋白激酶(ROCK)抑制剂在角膜疾病治疗中的药理学特性、治疗潜力和相关风险。本文重点介绍了四种关键的 ROCK 抑制剂:Y-27632、法舒地尔、利帕地尔和那他地尔,并进行了比较研究。支持 ROCK 抑制剂应用的研究强调了它们在各种角膜疾病中的疗效。在 Fuchs 内皮角膜营养不良中,Y-27632、利帕地尔和那他地尔的应用研究表明,角膜透明度、内皮细胞密度和视力均有显著提高。在假性晶状体囊泡性角膜病变中,将 Y-27632 与培养的角膜内皮细胞一起注射到前房,可提高角膜内皮细胞密度和改善视力。模拟角膜化学损伤的动物模型显示,应用法舒地尔后,新生血管形成和上皮缺损减少,在虹膜角膜内皮综合征的病例中,那他地尔可改善角膜水肿。在考虑安全性方面,两种已在临床上批准的药物那他地尔和利帕地尔都有不良反应,如结膜充血、结膜下出血、角膜卷丝状、结膜炎和睑缘炎。在治疗过程中监测患者对平衡潜在的治疗益处与这些相关风险至关重要。总之,ROCK 抑制剂,特别是那他地尔和利帕地尔,在治疗角膜疾病方面具有潜力。对其药理学特性的比较分析以及支持其疗效的研究强调了它们潜在的治疗意义。然而,需要进行持续的研究以全面了解它们在不同角膜疾病中的安全性概况和长期结果,从而指导它们在临床实践中的最佳应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f93/10804875/932f610de2ee/DDDT-18-97-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f93/10804875/d30b20acc2b5/DDDT-18-97-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f93/10804875/932f610de2ee/DDDT-18-97-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f93/10804875/d30b20acc2b5/DDDT-18-97-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f93/10804875/932f610de2ee/DDDT-18-97-g0002.jpg

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[1]
The Role of Rho Kinase Inhibitors in Corneal Diseases.

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[2]
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[3]
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[5]
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[6]
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[7]
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引用本文的文献

[1]
Therapeutic Potential of Rho Kinase Inhibitors in Corneal Disease: A Systematic Review of Preclinical and Clinical Studies.

Biomedicines. 2025-6-30

[2]
Safety, Tolerability, and Pharmacokinetics of NRL-1049, a Rho-Associated Kinase Inhibitor, in Healthy Volunteers: A Phase 1, First-in-Human, Single-Ascending Dose, Randomized, Placebo-Controlled Trial.

CNS Drugs. 2025-7-8

[3]
Current concepts and recent trends in endothelial keratoplasty.

World J Transplant. 2025-6-18

[4]
Rho-Kinase Inhibitors in the Management of Fuchs Endothelial Corneal Dystrophy: A Review.

Medicina (Kaunas). 2025-4-22

[5]
Managing pseudophakic bullous keratopathy with a topical rho kinase inhibitor: a case series.

J Med Case Rep. 2025-5-8

[6]
Rho Kinase Inhibitors in Glaucoma Management: Current Perspectives and Future Directions.

Drug Des Devel Ther. 2025-4-2

[7]
Drug- and Cell-Type-Specific Effects of ROCK Inhibitors as a Potential Cause of Reticular Corneal Epithelial Edema.

Cells. 2025-2-11

[8]
Available Therapeutic Options for Corneal Neovascularization: A Review.

Int J Mol Sci. 2024-5-17

本文引用的文献

[1]
ROCK inhibitors in ophthalmology: A critical review of the existing clinical evidence.

Clin Exp Ophthalmol. 2023-7

[2]
A systematic review on the effects of ROCK inhibitors on proliferation and/or differentiation in human somatic stem cells: A hypothesis that ROCK inhibitors support corneal endothelial healing via acting on the limbal stem cell niche.

Ocul Surf. 2023-1

[3]
Corneal endothelial wound healing: understanding the regenerative capacity of the innermost layer of the cornea.

Transl Res. 2022-10

[4]
Reticular epithelial corneal edema as a novel side-effect of Rho Kinase Inhibitors: An Indian scenario.

Indian J Ophthalmol. 2022-4

[5]
Rho-Associated Kinase Inhibitor Eye Drops in challenging cataract surgery.

Am J Ophthalmol Case Rep. 2021-12-16

[6]
A Close Look at the Clinical Efficacy of Rho-Associated Protein Kinase Inhibitor Eye Drops for Fuchs Endothelial Corneal Dystrophy.

Cornea. 2021-10-1

[7]
The Additive Effect of ROCK Inhibitor on Prostaglandin-Treated Japanese Patients with Glaucoma Indicating 15 mmHg and Under: ROCK U-15.

Adv Ther. 2021-7

[8]
Gene Therapy in the Anterior Eye Segment.

Curr Gene Ther. 2022

[9]
Harnessing the tunable cavity of nanoceria for enhancing Y-27632-mediated alleviation of ocular hypertension.

Theranostics. 2021-3-13

[10]
Pilot Study of Corneal Clearance With the Use of a Rho-Kinase Inhibitor After Descemetorhexis Without Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy.

Cornea. 2021-7-1

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