Ripasudil does not induce phospholipid accumulation in human corneal epithelial cells

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research Pub Date : 2025-03-20 DOI:10.1016/j.exer.2025.110351

Fumiko Tazoe , Yuichiro Watanabe , Noriyuki Inoue , Mizuho Kanazawa , Atsushi Kasano , Toshihiro Inoue

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引用次数: 0

Abstract

Rho-associated coiled-coil-containing protein kinase (Rho kinase; ROCK) inhibitors represent a novel class of glaucoma medications that lower intraocular pressure by enhancing aqueous humor outflow through the conventional outflow pathway. Netarsudil, a ROCK inhibitor, is known to induce cornea verticillata as an adverse effect in clinical settings. Unlike systemic amiodarone and antimalarials, topical agents do not typically induce the development of this corneal condition. This study investigated whether ripasudil, another ROCK inhibitor, induces cornea verticillata using a Chinese hamster-derived ovary cell line (CHO-K1), SV40 transformed human corneal epithelial cell line (HCE-T), and normal human primary corneal epithelial cells (HCEC-2). CHO-K1, HCE-T, and HCEC-2 were treated with ripasudil, netarsudil, or Y-27632 with varying concentrations (0.1, 0.3, 1, 3, 10, or 30 μM). Ripasudil and Y-27632 did not alter intracellular phospholipid levels at any concentration tested. Conversely, intracellular phospholipid accumulation was observed in cells treated with netarsudil. Netarsudil possesses chemical characteristics similar to those of cationic amphiphilic drugs, which are known to cause phospholipidosis. In contrast, ripasudil and Y-27632 lack these structural features. Our results suggest that ripasudil has a low likelihood of inducing cornea verticillata.

查看原文本刊更多论文

利帕舒地尔不会诱导人角膜上皮细胞的磷脂积累。

Rho激酶；ROCK抑制剂是一种新型的青光眼药物，通过增强房水通过常规流出途径流出来降低眼压。奈沙地尔是一种ROCK抑制剂，已知在临床环境中会引起角膜黄斑。与全身胺碘酮和抗疟药不同，局部用药通常不会诱发这种角膜状况的发展。本研究利用中国地鼠卵巢细胞系CHO-K1、SV40转化的人角膜上皮细胞系HCE-T和正常人原代角膜上皮细胞hcec2，研究了另一种ROCK抑制剂利帕舒地尔是否诱导角膜鸡斑。CHO-K1、HCE-T和hce -2分别用不同浓度（0.1、0.3、1、3、10或30 μM）的利帕舒地尔、奈沙地尔或Y-27632治疗。利帕舒地尔和Y-27632在任何浓度下都没有改变细胞内磷脂水平。相反，在用奈沙地尔处理的细胞中观察到细胞内磷脂积累。奈沙地尔具有与阳离子两亲性药物相似的化学特性，而阳离子两亲性药物已知会引起磷脂中毒。相比之下，利帕舒地尔和Y-27632缺乏这些结构特征。我们的研究结果表明，利帕舒地尔有低的可能性诱发鸡周性角膜。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental eye research 医学-眼科学

CiteScore

6.80

自引率

5.90%

发文量

323

审稿时长

66 days

期刊介绍： The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.