The Effects of ROCK Inhibitor on Prevention of Dexamethasone-Induced Glaucoma Phenotype in Human Trabecular Meshwork Cells.
The Effects of ROCK Inhibitor on Prevention of Dexamethasone-Induced Glaucoma Phenotype in Human Trabecular Meshwork Cells.
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DOI：
10.1167/tvst.12.12.4
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发表时间：
2023-12-01
影响因子：
3
通讯作者：
Park, Yoonjee C.
中科院分区：
文献类型：
--
作者：
Debele, Tilahun Ayane;Mount, Zachary F.;Yuan, Yong;Kao, WinstonW. -Y.;Park, Yoonjee C.
本研究研究了地塞米松 (Dex) 对人小梁网 (TM) 细胞（糖皮质激素诱导的青光眼模型）的影响，并评估了利帕舒地尔 (Rip) 作为联合给药或序贯给药策略的影响。进行体外实验来评估 Dex 和 Rip 对 TM 细胞的影响。使用共聚焦显微镜评估 Dex 和 Rip 对 F-肌动蛋白染色信号的影响。使用胶原凝胶收缩测定对模拟共同递送和顺序递送的 TM 细胞在 Dex 和 Rip 处理后的收缩性进行量化。还测量了跨上皮电阻 (TEER) 值和异硫氰酸荧光素 (FITC)-葡聚糖渗透性，以评估 Dex 和 Rip 对 TM 细胞的影响。 Dex 和 Rip 在最大测试浓度 (20 µM) 下未表现出细胞毒性。与对照组相比，Dex 处理的 TM 细胞表现出更高的 F-肌动蛋白染色信号，而与 Rip 共同处理时该信号降低。 Rip 在联合给药和序贯治疗中均抑制 Dex 诱导的胶原凝胶收缩活性。随着剂量的增加，Dex 导致 TEER 值增加，而与 Rip 共同治疗时 TEER 值保持不变。当患者接受 Dex 治疗时，联合给药 Rip 有可能预防青光眼症状。这项研究强调了在治疗各种疾病时确定减少长期使用糖皮质激素（例如 Dex）副作用的策略的重要性。这项研究证明了利帕舒地尔与地塞米松共同给药可减轻糖皮质激素引起的高眼压和类似于原发性开角型青光眼的继发性青光眼，为临床护理中新型预防策略的开发提供见解。
This study investigated the effects of dexamethasone (Dex) on human trabecular meshwork (TM) cells, a model of glucocorticoid-induced glaucoma, and evaluated the impact of ripasudil (Rip) as a co-delivery or sequential dosing strategy. In vitro experiments were conducted to assess the effects of Dex and Rip on TM cells. Confocal microscopy was used to evaluate the impact of Dex and Rip on F-actin staining signals. Contractility of the TM cells upon Dex and Rip treatment mimicking co-delivery and sequential delivery was quantified using collagen gel contraction assay. Transepithelial electrical resistance (TEER) values and fluorescein isothiocyanate (FITC)–dextran permeability were also measured to assess the impact of Dex and Rip on TM cells. Dex and Rip did not exhibit cytotoxicity at the maximum tested concentration (20 µM). Dex-treated TM cells exhibited higher F-actin staining signals compared to controls, which were reduced when co-treated with Rip. Rip inhibited Dex-induced collagen gel contraction activity in both co-delivery and sequential treatments. Dex resulted in increased TEER values as the dose increased, whereas TEER values were maintained when co-treated with Rip. Co-delivery of Rip has the potential to prevent glaucoma symptoms when patients are treated with Dex. This study highlights the importance of identifying strategies to reduce the side effects of prolonged use of glucocorticoids, such as Dex, in the treatment of various diseases. This study demonstrates the potential of co-delivering ripasudil with dexamethasone to mitigate glucocorticoid-induced ocular hypertension and a secondary glaucoma that resembles primary open-angle glaucoma, providing insights for the development of novel preventive strategies in clinical care.
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影响因子：
--
作者：
Singh K;Singh A
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
4.6
作者：
Ota C;Ida Y;Ohguro H;Hikage F
通讯作者：
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