Rho-kinase Inhibitors in Ocular Diseases: A Translational Research Journey.
Rho-kinase Inhibitors in Ocular Diseases: A Translational Research Journey.
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DOI：
10.5005/jp-journals-10078-1396
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发表时间：
2023-01
影响因子：
--
通讯作者：
Singh A
中科院分区：
文献类型：
--
作者：
Singh K;Singh A
本文综述了Rho激酶（ROCK）抑制剂在眼部疾病（主要是青光眼）中的应用。在过去的十年中，以ROCK抑制剂的开发为高潮的转化研究为青光眼药典提供了急需的一剂强心针。ROCK通路复杂地参与细胞骨架调节，其作用于细胞形态、细胞运动、细胞粘附、细胞凋亡和平滑肌收缩。这种细胞骨架调节特性已被用于改变小梁网（TM）阻力，导致ROCK抑制剂的发现，以增加小梁流出。综述了ROCK抑制剂用于抗青光眼药物治疗的多中心试验。重点是将这些药物的药理作用与临床效用联系起来。Rho激酶升高眼内压（IOP）治疗（ROCKET）试验比较了ROCK抑制剂奈他舒地尔与噻吗洛尔的单药治疗，MERCURY试验比较了拉坦前列素和ROCK抑制剂奈他舒地尔的固定剂量复方制剂[奈他舒地尔-拉坦前列素固定复方制剂（FCNL）]与任一种或比马前列素-噻吗洛尔复方制剂的单药治疗。虽然ROCKET试验显示ROCK抑制剂不劣于噻吗洛尔，但MERCURY试验显示FCNL实现的IOP降低比单药治疗更大。结膜充血是使用ROCK抑制剂报告的最常见副作用。ROCK抑制剂的中等疗效与结膜充血的常见副作用，使其成为一种可选择的抗青光眼药物，而不是一线治疗。与减少房水分泌或增强葡萄膜巩膜流出的现有抗青光眼药物相比，ROCK抑制剂对患病TM的作用更具生理性。ROCK抑制剂稳定视网膜血管和角膜内皮的特性为糖尿病视网膜病变和角膜失代偿的治疗开辟了新的篇章。Singh K，Singh A. Rho激酶抑制剂在眼部疾病中的应用：转化研究之旅。J Curr Glaucoma Pract 2023;17（1）：44-48.
This review summarizes current data on Rho-kinase (ROCK) inhibitors use in ocular diseases, primarily glaucoma. Translational research over the last decade culminating in the development of ROCK inhibitors has provided a much-needed shot in the arm to glaucoma pharmacopeia. ROCK pathway is intricately involved in cytoskeletal modulation with action on cell morphology, cell motility, cell adhesion, cell apoptosis, and smooth muscle contraction. This cytoskeletal modulation property has been utilized to modify trabecular meshwork (TM) resistance, resulting in the discovery of ROCK inhibitors to increase trabecular outflow. Multicentric trials on ROCK inhibitors for antiglaucoma medications are summarized. The focus is on linking pharmacological action to the clinical utility of these drugs. While the Rho Kinase Elevated intraocular Pressure (IOP) Treatment (ROCKET) trials compared monotherapy with ROCK inhibitor netarsudil vs timolol, MERCURY trials compared a fixed dose combination of latanoprost and ROCK inhibitor netarsudil [fixed combination netarsudil-latanoprost (FCNL)] vs monotherapy with either and bimatoprost-timolol combination. While ROCKET trials showed ROCK inhibitors to be non-inferior to timolol, MERCURY trials showed FCNL achieving a much greater IOP reduction than monotherapy with either. Conjunctival hyperemia was the most common side effect reported with ROCK inhibitor use. Moderate efficacy of ROCK inhibitors with a common side effect of conjunctival hyperemia, makes it an adjunctive antiglaucoma drug of choice and not a first-line therapy ROCK inhibitors’ action on diseased TM is more physiological compared to available antiglaucoma medications that either reduce aqueous secretion or enhance uveoscleral outflow. The property of ROCK inhibition to stabilize the endothelium of both retinal vasculature and cornea has opened a new chapter in the treatment of diabetic retinopathy and corneal decompensation. Singh K, Singh A. Rho-kinase Inhibitors in Ocular Diseases: A Translational Research Journey. J Curr Glaucoma Pract 2023;17(1):44-48.