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Potential Biomarkers for Primary Open-Angle Glaucoma Identified by Long Noncoding RNA Profiling in the Aqueous Humor

Authors :
Zhang Lusi
Bing Jiang
Cong Wang
Zheng Pan
Jingming Shi
Duan Xuanchu
Mao Mao
Songbo Jia
Lili Xie
Source :
The American Journal of Pathology. 189:739-752
Publication Year :
2019
Publisher :
Elsevier BV, 2019.

Abstract

This study aimed to identify potential biomarkers for primary open-angle glaucoma (POAG) diagnosis. First, long noncoding RNA (lncRNA) and mRNA expression profiles in the aqueous humor (AH) from 10 POAG and 10 control patients were accessed by microarray analyses. Coding-noncoding gene coexpression networks were drawn to predict potential lncRNA functions. lncRNA T267384, ENST00000607393, and T342877 expression levels were further tested by real-time quantitative PCR in AH from 29 POAG and 30 cataract patients, in iris tissues from 16 POAG patients and 10 controls, and in plasma from 49 POAG patients and 55 healthy controls. Finally, ENST00000607393 function was characterized in an in vitro model of cell calcification. A total of 3627 lncRNAs and 2228 mRNAs in the AH of POAG patients were significantly up-regulated, and 1520 lncRNAs and 820 mRNAs were significantly down-regulated. Seven lncRNAs showed positive correlation with glaucoma-associated gene, bone morphogenetic protein 2. Moreover, real-time quantitative RT-PCR confirmed that T267384, ENST00000607393, and T342877 expression levels were significantly higher in the AH from a different cohort of POAG patients. ENST00000607393 was also significantly higher in the iris and plasma of POAG patients. Last, ENST00000607393 knockdown alleviated calcification of primary human trabecular meshwork cells in vitro. Therefore, lncRNAs T267384, ENST00000607393, and T342877 may be potential biomarkers for POAG diagnosis. ENST00000607393 might be a new therapeutic target for trabecular meshwork calcification.

Details

ISSN :
00029440
Volume :
189
Database :
OpenAIRE
Journal :
The American Journal of Pathology
Accession number :
edsair.doi.dedup.....2e3d1bd7e36956d0e3d1eeb68cb70c08
Full Text :
https://doi.org/10.1016/j.ajpath.2018.12.011