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Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model

PURPOSE: 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. METHODS: DED...

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Autores principales: Chen, Yu, Pu, Jiheng, Li, Xinda, Lian, Lili, Ge, Chaoxiang, Liu, Zuimeng, Wang, Weizhuo, Hou, Ling, Chen, Wei, Li, Jinyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Association for Research in Vision and Ophthalmology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10029764/
https://www.ncbi.nlm.nih.gov/pubmed/36920364
http://dx.doi.org/10.1167/iovs.64.3.26
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author Chen, Yu
Pu, Jiheng
Li, Xinda
Lian, Lili
Ge, Chaoxiang
Liu, Zuimeng
Wang, Weizhuo
Hou, Ling
Chen, Wei
Li, Jinyang
author_facet Chen, Yu
Pu, Jiheng
Li, Xinda
Lian, Lili
Ge, Chaoxiang
Liu, Zuimeng
Wang, Weizhuo
Hou, Ling
Chen, Wei
Li, Jinyang
author_sort Chen, Yu
collection PubMed
description PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Aim2 deficiency alleviates ocular surface damage and LG inflammation in SCOP-induced DED.
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spelling pubmed-100297642023-03-22 Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model Chen, Yu Pu, Jiheng Li, Xinda Lian, Lili Ge, Chaoxiang Liu, Zuimeng Wang, Weizhuo Hou, Ling Chen, Wei Li, Jinyang Invest Ophthalmol Vis Sci Cornea PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Aim2 deficiency alleviates ocular surface damage and LG inflammation in SCOP-induced DED. The Association for Research in Vision and Ophthalmology 2023-03-15 /pmc/articles/PMC10029764/ /pubmed/36920364 http://dx.doi.org/10.1167/iovs.64.3.26 Text en Copyright 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Cornea
Chen, Yu
Pu, Jiheng
Li, Xinda
Lian, Lili
Ge, Chaoxiang
Liu, Zuimeng
Wang, Weizhuo
Hou, Ling
Chen, Wei
Li, Jinyang
Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model
title Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model
title_full Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model
title_fullStr Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model
title_full_unstemmed Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model
title_short Aim2 Deficiency Ameliorates Lacrimal Gland Destruction and Corneal Epithelium Defects in an Experimental Dry Eye Model
title_sort aim2 deficiency ameliorates lacrimal gland destruction and corneal epithelium defects in an experimental dry eye model
topic Cornea
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10029764/
https://www.ncbi.nlm.nih.gov/pubmed/36920364
http://dx.doi.org/10.1167/iovs.64.3.26
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