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单次前房内注射水凝胶建立的慢性高眼压大鼠模型的疗效、药物敏感性及安全性

Efficacy, Drug Sensitivity, and Safety of a Chronic Ocular Hypertension Rat Model Established Using a Single Intracameral Injection of Hydrogel into the Anterior Chamber.

作者信息

Yu Huan, Zhong Huimin, Chen Junjue, Sun Jun, Huang Ping, Xu Xing, Huang Shouyue, Zhong Yisheng

机构信息

Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiaotong University, Shanghai, China (mainland).

Shanghai Jiaotong University School of Medicine, Shanghai, China (mainland).

出版信息

Med Sci Monit. 2020 Sep 30;26:e925852. doi: 10.12659/MSM.925852.

Abstract

BACKGROUND Chronic ocular hypertension (COH) models mostly focus on changes in intraocular pressure (IOP) and loss of retinal ganglion cells (RGCs). The present study evaluated important glaucoma-related changes in visual function, response to common ocular hypotensive drugs, and safety for our previously developed rat model. MATERIAL AND METHODS The model was established through a single injection of hydrogel into the anterior chambers. Efficacy was assessed through F-VEP by measuring latency and amplitude of P1. We evenly divided 112 rats into 4 groups: control and COH at 2, 4, and 8 weeks. Response to 5 common drugs (brimonidine, timolol, benzamide, pilocarpine, and bimatoprost) were each tested on 6 rats and assessed using difference in IOP. Safety assessment was conducted through histological analysis of 24 rats evenly divided into 4 groups of control and COH at 2, 4, and 8 weeks. Corneal endothelial cells (CECs) of 24 additional rats were used to determine toxic effects through TUNEL and CCK-8 assays. RESULTS P1 latency and amplitude of VEP demonstrated the model is effective in inducing optic nerve function impairment. Only the drug pilocarpine failed to have an obvious hypotensive effect, while the other 4 were effective. CECs at 2, 4, and 8 weeks showed no significant differences from control groups in results of histological analysis, TUNEL, and CCK-8 assays. CONCLUSIONS A single injection of hydrogel into the anterior chamber is effective for modeling COH, can respond to most commonly used hypotensive drugs, and is non-toxic to the eyes.

摘要

背景

慢性高眼压(COH)模型大多聚焦于眼压(IOP)变化和视网膜神经节细胞(RGCs)丢失。本研究评估了我们先前建立的大鼠模型在视觉功能、对常用降眼压药物的反应及安全性方面与青光眼相关的重要变化。

材料与方法

通过向前房单次注射水凝胶建立模型。通过F-VEP测量P1的潜伏期和振幅来评估疗效。将112只大鼠平均分为4组:对照组以及2周、4周和8周的COH组。对6只大鼠分别测试5种常用药物(溴莫尼定、噻吗洛尔、苯甲酰胺、毛果芸香碱和比马前列素)的反应,并使用眼压差异进行评估。通过对24只大鼠进行组织学分析进行安全性评估,这些大鼠平均分为4组,分别为对照组以及2周、4周和8周的COH组。另外24只大鼠的角膜内皮细胞(CECs)用于通过TUNEL和CCK-8试验确定毒性作用。

结果

VEP的P1潜伏期和振幅表明该模型可有效诱导视神经功能损害。只有毛果芸香碱药物未产生明显的降压作用,而其他4种药物有效。2周、4周和8周时CECs在组织学分析、TUNEL和CCK-8试验结果中与对照组无显著差异。

结论

向前房单次注射水凝胶对COH建模有效,可对大多数常用降眼压药物产生反应,且对眼睛无毒。

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