Department of Microsurgery, Jesús Usón Minimally Invasive Surgery Centre, 10071, Cáceres, Spain.
Department of Biochemistry and Molecular Biology and Genetics, Faculty of Nursing and Occupational Therapy, University of Extremadura, Avda de La Universidad S/N, 10003, Cáceres, Spain.
Mol Cell Biochem. 2020 Nov;474(1-2):41-55. doi: 10.1007/s11010-020-03832-5. Epub 2020 Jul 24.
Autophagy is an intracellular catabolic process implicated in the recycling and degradation of intracellular components. Few studies have defined its role in corneal pathologies. Animal models are essential for understanding autophagy regulation and identifying new treatments to modulate its effects. A systematic review (SR) was conducted of studies employing animal models for investigations of autophagy in corneal diseases. Studies were identified using a structured search strategy (TS = autophagy AND cornea*) in Web of Science, Scopus, and PubMed from inception to September 2019. In this study, 230 articles were collected, of which 28 were analyzed. Mouse models were used in 82% of the studies, while rat, rabbit, and newt models were used in the other 18%. The most studied corneal layer was the epithelium, followed by the endothelium and stroma. In 13 articles, genetically modified animal models were used to study Fuch endothelial corneal dystrophy (FECD), granular corneal dystrophy type 2 (GCD2), dry eye disease (DED), and corneal infection. In other 13 articles, animal models were experimentally induced to mimic DED, keratitis, inflammation, and surgical scenarios. Furthermore, in 50% of studies, modulators that activated or inhibited autophagy were also investigated. Protective effects of autophagy activators were demonstrated, including rapamycin for DED and keratitis, lithium for FECD, LYN-1604 for DED, cysteamine and miR-34c antagomir for damaged corneal epithelium. Three autophagy suppressors were also found to have therapeutic effects, such as aminoimidazole-4-carboxamide-riboside (AICAR) for corneal allogeneic transplantation, celecoxib and chloroquine for DED.
自噬是一种细胞内的分解代谢过程，参与细胞内成分的回收和降解。很少有研究定义了它在角膜病变中的作用。动物模型对于理解自噬的调节以及确定新的治疗方法来调节其作用至关重要。本研究对使用动物模型研究角膜疾病中自噬的研究进行了系统评价（SR）。通过在 Web of Science、Scopus 和 PubMed 中使用结构化的搜索策略（TS=自噬 AND 角膜*），从成立到 2019 年 9 月，对研究进行了识别。在这项研究中，共收集了 230 篇文章，其中分析了 28 篇。在 82%的研究中使用了小鼠模型，而在其余 18%的研究中使用了大鼠、兔和蝾螈模型。研究最多的角膜层是上皮，其次是内皮和基质。在 13 篇文章中，使用了基因修饰的动物模型来研究 Fuch 内皮角膜营养不良（FECD）、颗粒状角膜营养不良 2 型（GCD2）、干眼症（DED）和角膜感染。在其他 13 篇文章中，动物模型被实验诱导以模拟 DED、角膜炎、炎症和手术情况。此外，在 50%的研究中，还研究了激活或抑制自噬的调节剂。自噬激活剂的保护作用得到了证实，包括雷帕霉素治疗 DED 和角膜炎、锂治疗 FECD、LYN-1604 治疗 DED、半胱氨酸和 miR-34c 反义寡核苷酸治疗受损的角膜上皮。还发现了三种自噬抑制剂具有治疗作用，如氨基咪唑-4-羧酰胺-核苷（AICAR）治疗角膜同种异体移植、塞来昔布和氯喹治疗 DED。
