对局部和全身抗真菌药物的眼部安全性评估:多来源药物监测和基因组研究
Dangdang Wang1, Yang Peng1, Qi Zhang1
1Department of Ophthalmology, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
European journal of pharmacology
|August 28, 2025
概括
系统性抗真菌药物比局部药物具有更大的眼睛风险,可能导致严重的视力问题. 这项研究强调PI3K-Akt信号传递和CES1是抗真菌相关眼睛毒性的关键因素.
科学领域:
- 眼科 眼科
- 药物监督管理
- 基因组学
背景情况:
- 抗真菌药物用于真菌感染,但已知有眼部副作用.
- 抗真菌药物对眼睛的安全性尚未完全确定.
研究的目的:
- 调查与抗真菌药物相关的眼部不良事件.
- 探索这些眼部毒性的分子机制.
主要方法:
- 使用了FDA不良事件报告系统 (FAERS) 的数据 (2004-2024年).
- 进行不相称性分析,追溯临床数据验证和系统药理分析.
- 使用网络分析和基于总结数据的门德尔随机化 (SMR) 与状炎全基因组关联研究 (GWAS).
主要成果:
- 确定了71529个与抗真菌药物相关的AE报告.
- 系统性抗真菌药物与严重的视力威胁事件 (例如,有毒的视神经病变) 有关,而局部药物则与表面症状有关.
- 在PI3K-Akt和亡途径中发现了枢纽基因 (STAT3,AKT1,SRC),并确定了CES1作为与角质炎风险相关的基因.
结论:
- 与局部药物相比,全身抗真菌药物具有更广泛和更严重的眼部副作用.
- PI3K-Akt信号和CES1可能会调解抗真菌诱导的眼睛毒性.
- 这些发现为风险评估和机制理解提供了洞察力,需要进一步验证.
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