神经激肽-1 受体拮抗剂能减轻家兔模型中的非过敏性眼红。

IF 1.9 4区 医学 Q2 OPHTHALMOLOGY Journal of Ocular Pharmacology and Therapeutics Pub Date : 2024-09-01 Epub Date: 2024-06-03 DOI:10.1089/jop.2024.0003
Lingjia Liu, Shudan Wang, Tomas Blanco, Hongyan Ge, Shuyan Zhu, Jia Yin, Yihe Chen, Reza Dana
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引用次数: 0

摘要

目的:评估局部应用神经激肽-1 受体(NK1R)拮抗剂在非过敏性眼红兔模型中的疗效。方法:在兔非过敏性眼红模型中局部应用神经激肽-1 受体 (NK1R) 拮抗剂:单次局部使用盐酸达哌泊唑滴眼液(0.5%、1%、2% 或 5%)诱导兔子出现非过敏性眼红。在诱导的同时或诱导后 20 分钟将 NK1R 拮抗剂 L-703,606 局部滴眼,磷酸盐缓冲盐水 (PBS) 处理作为对照。用基于 ImageJ 的眼红指数(ORI)计算方法在图像上评估眼红的严重程度。结果在每个评估时间点使用 0.5%、1%、2% 或 5%的达哌唑后,ORI 分数都会显著增加,其中 5%的达哌唑诱导的眼红最为严重,在诱导后 20 分钟时 ORI 分数的最大平均值增加了 14 分,因此可用于随后评估 NK1R 拮抗剂的疗效。在诱导达哌拉唑的同时使用外用 L-703,606,可显著抑制所有时间点 ORI 分数的增加(减少 40%)。此外,在达比拉唑诱导后 20 分钟使用 L-703,606,可迅速有效地抑制 ORI 评分在 30、40、50 和 60 分钟的增加(减少 30%)。结论在一种新型动物模型中,局部阻断 NK1R 可有效预防和缓解非过敏性眼红。
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Neurokinin-1 Receptor Antagonism Reduces Nonallergic Ocular Redness in a Rabbit Model.

Purpose: To evaluate the therapeutic efficacy of topical application of a neurokinin-1 receptor (NK1R) antagonist in a rabbit model of nonallergic ocular redness. Methods: Nonallergic ocular redness was induced in rabbits by a single, topical application of dapiparzole hydrochloride eye drops (0.5%, 1%, 2%, or 5%). The NK1R antagonist L-703,606 was topically applied to the eye at the same time of induction or 20 min after induction, and phosphate buffered saline (PBS) treatment served as the control. Superior bulbar conjunctival images were taken every 30 s for the first 2 min, followed by every 4 min for 8 min, and then every 10 min until 1 h. The severity of ocular redness was evaluated on the images using ImageJ-based ocular redness index (ORI) calculations. Results: The ORI scores were significantly increased after the application of 0.5%, 1%, 2%, or 5% dapiparzole at each time point evaluated, with the most severe redness induced by the 5% dapiprazole that led to a maximal mean increase in ORI score of 14 at 20 min post-induction and thus used for subsequent evaluation of therapeutic efficacy of NK1R antagonism. Topical L-703,606, when applied at the same time as dapiprazole induction, significantly suppressed the increase of ORI scores at all time points (∼40% decrease). Furthermore, when applied at 20 min after dapiprazole induction, L-703,606 rapidly and effectively suppressed the increase of ORI scores at 30, 40, 50, and 60 min (∼30% decrease). Conclusions: Topical blockade of NK1R effectively prevents and alleviates nonallergic ocular redness in a novel animal model.

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来源期刊
CiteScore
4.60
自引率
4.30%
发文量
72
审稿时长
1 months
期刊介绍: Journal of Ocular Pharmacology and Therapeutics is the only peer-reviewed journal that combines the fields of ophthalmology and pharmacology to enable optimal treatment and prevention of ocular diseases and disorders. The Journal delivers the latest discoveries in the pharmacokinetics and pharmacodynamics of therapeutics for the treatment of ophthalmic disorders. Journal of Ocular Pharmacology and Therapeutics coverage includes: Glaucoma Cataracts Retinal degeneration Ocular infection, trauma, and toxicology Ocular drug delivery and biotransformation Ocular pharmacotherapy/clinical trials Ocular inflammatory and immune disorders Gene and cell-based therapies Ocular metabolic disorders Ocular ischemia and blood flow Proliferative disorders of the eye Eyes on Drug Discovery - written by Gary D. Novack, PhD, featuring the latest updates on drug and device pipeline developments as well as policy/regulatory changes by the FDA.
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