角膜缘干细胞缺乏的动物模型:批判性叙述性文献综述
Animal Models for Limbal Stem Cell Deficiency: A Critical Narrative Literature Review.
作者信息
Atalay Eray, Altuğ Burcugül, Çalışkan Mert Egemen, Ceylan Semih, Özler Zeynep Serra, Figueiredo Gustavo, Lako Majlinda, Figueiredo Francisco
机构信息
Department of Ophthalmology, Eskişehir Osmangazi University Medical School, Eskişehir, Turkey.
Cellular Therapy and Stem Cell Production Application, Research Centre (ESTEM), Eskişehir Osmangazi University, Eskişehir, Turkey.
出版信息
Ophthalmol Ther. 2024 Mar;13(3):671-696. doi: 10.1007/s40123-023-00880-0. Epub 2024 Jan 27.
This literature review will provide a critical narrative overview of the highlights and potential pitfalls of the reported animal models for limbal stem cell deficiency (LSCD) and will identify the neglected aspects of this research area. There exists significant heterogeneity in the literature regarding the methodology used to create the model and the predefined duration after the insult when the model is supposedly fully fit for evaluations and/or for testing various therapeutic interventions. The literature is also replete with examples wherein the implementation of a specific model varies significantly across different studies. For example, the concentration of the chemical, as well as its duration and technique of exposure in a chemically induced LSCD model, has a great impact not only on the validity of the model but also on the severity of the complications. Furthermore, while some models induce a full-blown clinical picture of total LSCD, some are hindered by their ability to yield only partial LSCD. Another aspect to consider is the nature of the damage induced by a specific method. As thermal methods cause more stromal scarring, they may be better suited for assessing the anti-fibrotic properties of a particular treatment. On the other hand, since chemical burns cause more neovascularisation, they provide the opportunity to tap into the potential treatments for anti-neovascularisation. The animal species (i.e., rats, mice, rabbits, etc.) is also a crucial factor in the validity of the model and its potential for clinical translation, with each animal having its unique set of advantages and disadvantages. This review will also elaborate on other overlooked aspects, such as the anaesthetic(s) used during experiments, the gender of the animals, care after LSCD induction, and model validation. The review will conclude by providing future perspectives and suggestions for further developments in this rather important area of research.
本综述将对已报道的角膜缘干细胞缺乏(LSCD)动物模型的亮点和潜在缺陷进行批判性叙述概述,并确定该研究领域中被忽视的方面。在文献中,关于创建模型所使用的方法以及损伤后假定模型完全适合评估和/或测试各种治疗干预措施的预定义持续时间,存在显著的异质性。文献中还充斥着这样的例子,即特定模型的实施在不同研究中差异很大。例如,在化学诱导的LSCD模型中,化学物质的浓度及其暴露持续时间和技术,不仅对模型的有效性有很大影响,而且对并发症的严重程度也有很大影响。此外,虽然一些模型可诱发完全成熟的全角膜缘干细胞缺乏临床症状,但有些模型仅能产生部分角膜缘干细胞缺乏,从而受到限制。另一个需要考虑的方面是特定方法所诱导损伤的性质。由于热方法会导致更多的基质瘢痕形成,它们可能更适合评估特定治疗的抗纤维化特性。另一方面,由于化学烧伤会导致更多的新生血管形成,它们为开发抗新生血管形成的潜在治疗方法提供了机会。动物物种(如大鼠、小鼠、兔子等)也是模型有效性及其临床转化潜力的关键因素,每种动物都有其独特的优缺点。本综述还将阐述其他被忽视的方面,如实验过程中使用的麻醉剂、动物的性别、角膜缘干细胞缺乏诱导后的护理以及模型验证。综述将通过提供未来展望和对这一相当重要的研究领域进一步发展的建议来结束。