目的:动物模型是阐明病理生理机制和评价新疗法的关键。本系统综述确定了开发或适应角膜缘干细胞缺乏症(LSCD)动物模型的研究,评估他们的报告质量,总结了它们的关键特征,并建立了它们与人类疾病的临床转化相关性。
方法:该方案是前瞻性注册的(PROSPEROCRD42020203937)。搜索是在PubMed中进行的,OvidEMBASE和WebofScience于2020年8月发布。两位作者筛选了引文,提取的数据,使用ARRIVE指南评估符合条件的研究的报告质量,并使用自定义矩阵判断每个模型的临床转化相关性。
结果:纳入105项研究。兔子是最常见的动物。总的来说,97%的研究将LSCD概括为临床病因,然而,62%的人没有提供足够的方法学细节来实现模型的独立复制。不良事件和/或排除动物的报道很少(20%)。大约四分之一的研究没有产生预期的LSCD严重程度;34%提供的信息不足以评估疾病诱导的保真度。在13%的研究中进行了LSCD诱导的辅助诊断确认。
结论:这是首次评估LSCD动物模型的报告质量和临床转化相关性的系统评价。LSCD的模型随着时间的推移而发展,导致动物特征的可变报告,实验程序和不良事件。在大多数研究中,LSCD的验证使用临床测试;较新的辅助技术将增强诊断验证.由于大多数研究试图评估LSCD的新疗法,动物模型应理想地概括患者中发展的病症的所有特征。
OBJECTIVE: Animal models are pivotal for elucidating pathophysiological mechanisms and evaluating novel therapies. This systematic
review identified studies that developed or adapted animal models of limbal stem cell deficiency (LSCD), assessed their reporting quality, summarized their key characteristics, and established their clinical translational relevance to human disease.
METHODS: The protocol was prospectively registered (PROSPERO CRD42020203937). Searches were conducted in PubMed, Ovid EMBASE and Web of Science in August 2020. Two authors screened citations, extracted data, assessed the reporting quality of eligible studies using the ARRIVE guidelines, and judged the clinical translational relevance of each model using a custom matrix.
RESULTS: 105 studies were included. Rabbits were the most common animal species. Overall, 97% of studies recapitulated LSCD to a clinical etiology, however 62% did not provide sufficient methodological detail to enable independent reproduction of the model. Adverse events and/or exclusion of animals were infrequently (20%) reported. Approximately one-quarter of studies did not produce the intended severity of LSCD; 34% provided insufficient information to assess the fidelity of disease induction. Adjunctive diagnostic confirmation of LSCD induction was performed in 13% of studies.
CONCLUSIONS: This is the first systematic
review to assess the reporting quality and clinical translational relevance of animal models of LSCD. Models of LSCD have evolved over time, resulting in variable reporting of the characteristics of animals, experimental procedures and adverse events. In most studies, validation of LSCD was made using clinical tests; newer adjunctive techniques would enhance diagnostic validation. As most studies sought to evaluate novel therapies for LSCD, animal models should ideally recapitulate all features of the condition that develop in patients.