Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model.
Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model.
复制标题
Aim2缺陷改善实验性干眼模型中的泪腺破坏和角膜上皮缺损。
DOI：
10.1167/iovs.64.3.26
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发表时间：
2023-03-01
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
干眼病（DED）是一种与炎症相关的多因素疾病。在DED患者的泪液中存在过量的DNA。黑色素瘤2 （AIM2）缺失是一个关键的DNA传感器。本研究旨在探讨AIM2在DED发病机制中的作用。采用注射东莨菪碱（SCOP）诱导DED。采用游离DNA (cfDNA) ELISA和免疫染色检测异常DNA。采用角膜荧光素染色、封闭带-1免疫染色和TUNEL评价角膜上皮缺损。用酚红线试验分析了产泪量。采用苏木精染色、伊红染色及透射电镜检查泪腺组织学。免疫组化检测巨噬细胞标志物F4/80在LG的浸润情况。RT-qPCR分析基因表达。用免疫印迹法或ELISA法检测蛋白的产生。Aim2−/−小鼠在正常条件下LG和角膜的结构和功能正常。在scopo诱导的DED中，野生型（WT）小鼠泪液中cfDNA增加，dsDNA的异常积累伴随着LG中AIM2表达的增加。在scopo诱导的DED中，WT小鼠显示LG结构受损，泪液分泌减少，角膜上皮严重缺损，而Aim2−/−小鼠的LG结构保存较好，泪液分泌减少较少，干眼临床症状改善。此外，Aim2基因缺失抑制了scopo诱导的DED中巨噬细胞浸润的增加，抑制了N-GSDMD和il - 18的产生。Aim2缺乏可减轻scopd性DED的眼表损伤和LG炎症。
Dry eye disease (DED) is a multifactorial disease that is associated with inflammation. Excessive DNA is present in the tear fluid of patients with DED. Absent in melanoma 2 (AIM2) is a key DNA sensor. This study aimed to investigate the role of AIM2 in the pathogenesis of DED. DED was induced by injection of scopolamine (SCOP). Aberrant DNA was detected by cell-free DNA (cfDNA) ELISA and immunostaining. Corneal epithelial defects were assessed by corneal fluorescein staining, zonula occludens-1 immunostaining and TUNEL. Tear production was analyzed by phenol red thread test. Lacrimal gland (LG) histology was evaluated by hematoxylin and eosin staining, and transmission electron microscopy examination. Macrophage infiltration in LG was detected by immunohistochemistry for the macrophage marker F4/80. Gene expression was analyzed by RT-qPCR. Protein production was examined by immunoblot analysis or ELISA. Aim2−/− mice displayed a normal structure and function of LG and cornea under normal conditions. In SCOP-induced DED, wild type (WT) mice showed increased cfDNA in tear fluid, and aberrant accumulations of dsDNA accompanied by increased AIM2 expression in the LG. In SCOP-induced DED, WT mice displayed damaged structures of LG, reduced tear production, and severe corneal epithelium defects, whereas Aim2−/− mice had a better preserved LG structure, less decreased tear production, and improved clinical signs of dry eye. Furthermore, genetic deletion of Aim2 suppressed the increased infiltration of macrophages and inhibited N-GSDMD and IL18 production in the LG of SCOP-induced DED. Aim2 deficiency alleviates ocular surface damage and LG inflammation in SCOP-induced DED.
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影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
30.5
作者：
Buerckstuemmer, Tilmann;Baumann, Christoph;Superti-Furga, Giulio
通讯作者：
Superti-Furga, Giulio
影响因子：
44.1
作者：
Lian, Qiaoshi;Xu, Jun;Geng, Meiyu
通讯作者：
Geng, Meiyu
影响因子：
13.6
作者：
Komada, Takanori;Chung, Hyunjae;Muruve, Daniel A.
通讯作者：
Muruve, Daniel A.
影响因子：
64.8
作者：
Lammert CR;Frost EL;Bellinger CE;Bolte AC;McKee CA;Hurt ME;Paysour MJ;Ennerfelt HE;Lukens JR
通讯作者：
Lukens JR