The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye.
The transcriptome of rabbit conjunctiva in dry eye disease: Large-scale changes and similarity to the human dry eye.
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DOI：
10.1371/journal.pone.0254036
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Rigas B
中科院分区：
文献类型：
--
作者：
Master A;Kontzias A;Huang L;Huang W;Tsioulias A;Zarabi S;Wolek M;Wollocko BM;Honkanen R;Rigas B
干眼病(DED)的病理生理学在很大程度上仍不清楚，部分原因是缺乏成功的治疗方法。我们采用兔慢性DED模型，每周向眶周泪腺注射刀豆蛋白A 3次，探讨DED的病理生理学机制。使用微阵列和必要的确认性实时聚合酶链式反应检测DED兔和正常对照组的全层结膜组织的转录组。结果进行生物信息学分析。DED导致5,184个基因(占总数的22%)的基因转录发生大规模变化。差异表达的基因可以分为：功能模块和簇；改变的途径；功能连锁的基因；以及已知或怀疑与DED相关的单个基因组。这些亚群的一个共同特征是变化的广度和幅度，这些变化涵盖了眼睛免疫学和基本上细胞生物学的所有方面。突出的变化涉及先天性和获得性免疫反应；眼表炎症；至少25个显著改变的信号通路；大量的趋化因子；细胞周期和细胞凋亡。将我们的发现与与干燥综合征或非干燥综合征相关的DED患者现有的有限转录数据进行比较，发现人和兔的DED转录之间存在显著的相关性。我们的数据，建立了DED的大规模转录变化及其与人类的潜在相似性，强调了DED的巨大复杂性；建立了DED的强大动物模型；将有助于扩大我们对其病理生理学的理解；并可能指导成功的治疗策略的开发。
The pathophysiology of dry eye disease (DED) remains largely unknown, accounting in part for the lack of successful treatments. We explored the pathophysiology of DED using a rabbit model of chronic DED induced with 3 weekly injections of Concanavalin A into the periorbital lacrimal glands. The transcriptome of full-thickness’s conjunctival tissue from rabbits with DED and from normal controls was determined using microarrays and, as needed, confirmatory real-time polymerase chain reactions. Results were subjected to bioinformatic analysis. DED induced large-scale changes in gene transcription involving 5,184 genes (22% of the total). Differentially expressed genes could be segregated into: functional modules and clusters; altered pathways; functionally linked genes; and groups of individual genes of known or suspected pathophysiological relevance to DED. A common feature of these subgroups is the breadth and magnitude of the changes that encompass ocular immunology and essentially all aspects of cell biology. Prominent changes concerned innate and adaptive immune responses; ocular surface inflammation; at least 25 significantly altered signaling pathways; a large number of chemokines; cell cycle; and apoptosis. Comparison of our findings to the limited extant transcriptomic data from DED patients associated with either Sjogren’s syndrome or non-Sjogren’s etiologies revealed a significant correlation between human and rabbit DED transcriptomes. Our data, establishing the large-scale transcriptomic changes of DED and their potential similarity to the human, underscore the enormous complexity of DED; establish a robust animal model of DED; will help expand our understanding of its pathophysiology; and could guide the development of successful therapeutic strategies.
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影响因子：
2
作者：
Honkanen, Robert;Huang, Wei;Rigas, Basil
通讯作者：
Rigas, Basil
影响因子：
7.3
作者：
Kessal K;Liang H;Rabut G;Daull P;Garrigue JS;Docquier M;Melik Parsadaniantz S;Baudouin C;Brignole-Baudouin F
通讯作者：
Brignole-Baudouin F
影响因子：
4.4
作者：
Boehm, Nils;Funke, Sebastian;Grus, Franz H.
通讯作者：
Grus, Franz H.
影响因子：
2
作者：
Honkanen, Robert;Nemesure, Barbara;Rigas, Basil
通讯作者：
Rigas, Basil
影响因子：
3.4
作者：
Golebiowski, B.;Papas, E.;Stapleton, F.
通讯作者：
Stapleton, F.