Investigational Rho Kinase Inhibitors for the Treatment of Glaucoma.
Investigational Rho Kinase Inhibitors for the Treatment of Glaucoma.
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DOI：
10.2147/jep.s259297
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发表时间：
2021
影响因子：
--
通讯作者：
Kooner K
中科院分区：
文献类型：
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作者：
Al-Humimat G;Marashdeh I;Daradkeh D;Kooner K
本文综述了新型ROCK抑制剂作为一种降低青光眼眼内压（IOP）的创新治疗选择的最新进展，旨在描述每种药物的结构、作用机制、药物特性、理想的眼部效应，包括副作用。使用PubMed、Scopus、clinicaltrials.gov、ARVO期刊、科克伦图书馆和Selleckchem进行文献综述。使用“研究性Rho激酶抑制剂”和“青光眼”作为关键词检索数据库。除了这种构建块策略之外，还采用连续馏分来进一步细化结果。在发现的几种ROCK抑制剂中，目前只有两种药物被批准用于青光眼治疗;美国的Netarsudil和日本和中国的Ripasudil。我们确定并审查了目前在实验室或临床试验中的15种药物。这些药物主要通过小梁网（TM）细胞的药理学松弛降低外流阻力和降低巩膜外静脉压来降低IOP。它们具有乐观的安全性;然而，结膜充血、结膜出血、滴注疼痛和角膜轮动是常见的。其他特性，如神经保护（增强视神经血流和促进轴突再生），抗纤维化活性和内皮细胞增殖，可改善青光眼的视力预后和手术结果。此外，这些药物具有与其他局部青光眼药物协同作用的潜力。
This review provides a comprehensive update on emerging ROCK inhibitors as an innovative treatment option for lowering intraocular pressure (IOP) in glaucoma and aims to describe the structure, mechanism of action, pharmaceutical characteristics, desirable ocular effects, including side effects for each agent. A literature review was conducted using PubMed, Scopus, clinicaltrials.gov, ARVO journals, Cochrane library and Selleckchem. Databases were searched using “investigational Rho kinase inhibitors,” and “glaucoma” as keywords. In addition to this building block strategy, successive fractions were employed to further refine the results. Of the several ROCK inhibitors discovered, only two drugs are currently approved for glaucoma treatment; Netarsudil in the USA and Ripasudil in Japan and China. We identified and reviewed 15 agents currently in laboratory or clinical trials. These agents lower IOP mainly by decreasing outflow resistance through pharmacologic relaxation of the trabecular meshwork (TM) cells and reducing episcleral venous pressure. They have an optimistic safety profile; however, conjunctival hyperemia, conjunctival hemorrhage, pain on instillation, and corneal verticillata are common. Other properties such as neuroprotection (enhancing optic nerve blood flow and promoting axonal regeneration), anti-fibrotic activity, and endothelial cell proliferation may improve the visual prognosis and surgical outcomes in glaucoma. In addition, these agents have the potential to work synergistically with other topical glaucoma medications.