Delic Naomi C, Cai Jessie R, Watson Stephanie L, Downie Laura E, Di Girolamo Nick
School of Medical Sciences, Mechanisms of Disease and Translational Research, University of New South Wales, Sydney, New South Wales, 2052, Australia.
The University of Sydney, Save Sight Institute, Discipline of Ophthalmology, Sydney Medical School, Sydney, NSW, 2000, Australia.
Ocul Surf. 2022 Jan;23:169-183. doi: 10.1016/j.jtos.2021.09.006. Epub 2021 Sep 25.
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.
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.
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.
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.
动物模型对于阐明病理生理机制和评估新疗法至关重要。本系统评价确定了开发或改编角膜缘干细胞缺乏（LSCD）动物模型的研究，评估了其报告质量，总结了其关键特征，并确定了它们与人类疾病的临床转化相关性。
该方案已前瞻性注册（PROSPERO CRD42020203937）。2020年8月在PubMed、Ovid EMBASE和Web of Science中进行了检索。两名作者筛选了文献，提取了数据，使用ARRIVE指南评估了符合条件研究的报告质量，并使用自定义矩阵判断了每个模型的临床转化相关性。
纳入105项研究。兔子是最常见的动物物种。总体而言，97%的研究将LSCD概括为临床病因，然而62%的研究没有提供足够的方法细节以实现模型的独立复制。不良事件和/或动物排除情况报告较少（20%）。约四分之一的研究未产生预期的LSCD严重程度；34%的研究提供的信息不足以评估疾病诱导的保真度。13%的研究对LSCD诱导进行了辅助诊断确认。
这是第一项评估LSCD动物模型报告质量和临床转化相关性的系统评价。LSCD模型随时间不断演变，导致动物特征、实验程序和不良事件的报告存在差异。在大多数研究中，LSCD是通过临床测试进行验证的；更新的辅助技术将增强诊断验证。由于大多数研究旨在评估LSCD的新疗法，理想情况下动物模型应概括患者所患疾病的所有特征。
