Differential gene expression profiles of trabecular meshwork between POAG and non-POAG donated eyes by using RNA-sequencing

Authors: Liu Lifang,  Zeng Jinhui,  Huang Chukai,  Wang Geng,  Zhang Mingzhi

DOI: 10.3760/cma.j.cn115989-20191018-00451
Published 2020-08-10
Cite as Chin J Exp Ophthalmol, 2020,38(08): 646-652.

Abstract

Objective

To investigate gene basis of primary open angle glaucoma (POAG) by comparing gene expression profile of trabecular meshwork between POAG patients and normal controls by using RNA-sequencing.

Methods

Trabecular meshwork specimen were obtained from trabeculectomy (POAG group, n=3) or donated eyes (control group, n=2). RNA was extracted and sequenced in both groups, gene expression profiles were analyzed and compared between them, and different expression genes associated with POAG were revealed by using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Protein Analysis Through Evolutionary Relationships (PANTHER) gene list analysis.Written informed consent was obtained from each patient or the family members prior to entering the study cohort.The study protocol was approved by the Ethics Committee of Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong [No.EC20140311(3)-P01].

Results

(1)Total of 28 821 genes were obtained from RNA-sequencing, 22 genes were statistically significant between the two groups, of which one gene was up-regulated and 21 genes were down-regulated; (2)Genes that expressed differently had concentrated functions, biological process involved keratinization, epidermis development and intermediate filament cytoskeleton organization, cellular component related to keratin filament, intermediate filament, extracellular exosome and haptoglobin-hemoglobin complex, molecular function related to structural molecule activity and structural constituent of cytoskeleton; (3)Significantly enriched PANTHER pathways were plasminogen activating cascade, p38 MAPK pathway, oxidative stress response and p53 pathway.

Conclusions

Trabecular meshwork and extracellular matrix remodeling due to abnormal keratin expression, structural change of intermediate filament cytoskeleton and misregulation of plasminogen activating cascade, p38 MAPK pathway were possible etiology of POAG.Differential expressed genes that related to POAG mainly involve cytoskeleton associated genes and extracellular matrix remodeling genes.Thus, regulation of these genes may have an effect on glaucomatous treatment.

Key words:

Primary open angle glaucoma; Trabecular meshwork; RNA-sequencing

Contributor Information

Liu Lifang
Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China
Zeng Jinhui
Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China
Huang Chukai
Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China
Wang Geng
Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China
Zhang Mingzhi
Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Shantou 515041, China
(Read 249 times, 1 visits today)
Updated: August 19, 2020 — 9:28 am