Efficacy, Drug Sensitivity, and Safety of a Chronic Ocular Hypertension Rat Model Established Using a Single Intracameral Injection of Hydrogel into the Anterior Chamber.
Efficacy, Drug Sensitivity, and Safety of a Chronic Ocular Hypertension Rat Model Established Using a Single Intracameral Injection of Hydrogel into the Anterior Chamber.
复制标题
使用单次前房内注射水凝胶建立慢性高眼压大鼠模型的功效、药物敏感性和安全性
DOI：
10.12659/msm.925852
复制
发表时间：
2020-09-30
期刊：
影响因子：
--
通讯作者：
Zhong Y
中科院分区：
文献类型：
--
作者：
Yu H;Zhong H;Chen J;Sun J;Huang P;Xu X;Huang S;Zhong Y
背景慢性高眼压（COH）模型主要关注眼内压（IOP）的变化和视网膜神经节细胞（RGC）的缺失。本研究评估了重要的青光眼相关的视觉功能的变化，对常见的眼部消肿药物的反应，以及我们以前开发的大鼠模型的安全性。材料/方法通过一次性前房注射水凝胶建立模型。通过测量P1的潜伏期和振幅，通过F-VEP评估疗效。我们将112只大鼠平均分为4组：对照组和COH 2，4，8周。在6只大鼠上分别测试了对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IOP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组对照组和COH组，分别在第2、4和8周进行。另外24只大鼠的角膜内皮细胞（CEC）用于通过TUNEL和CCK-8测定来确定毒性作用。结果VEP的P1潜伏期和波幅显示该模型可有效诱导视神经功能损害。除毛果芸香碱无明显消肿作用外，其余4种药物均有效。CEC在第2、4和8周的组织学分析、TUNEL和CCK-8测定结果与对照组无显著差异。结论一次性前房注射水凝胶可有效地模拟COH，对常用的消肿药物有效，对眼无毒性。
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/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.