Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro

Abstract In the quest of identifying newer molecular targets for the management of glucocorticoid-induced ocular hypertension (GC-OHT) and glaucoma (GCG), several microarray studies have attempted to investigate the genome-wide transcriptome profiling of primary human trabecular meshwork (TM) cells...

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Main Authors: Kandasamy Kathirvel, Lester Karen, Ravinarayanan Haribalaganesh, Ramasamy Krishnadas, Veerappan Muthukkaruppan, Brian Lane, David A. Simpson, Kasia Goljanek-Whysall, Carl Sheridan, Devarajan Bharanidharan, Colin E. Willoughby, Srinivasan Senthilkumari
Format: Article
Language:English
Published: Nature Portfolio 2022-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-12443-7
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author Kandasamy Kathirvel
Lester Karen
Ravinarayanan Haribalaganesh
Ramasamy Krishnadas
Veerappan Muthukkaruppan
Brian Lane
David A. Simpson
Kasia Goljanek-Whysall
Carl Sheridan
Devarajan Bharanidharan
Colin E. Willoughby
Srinivasan Senthilkumari
author_facet Kandasamy Kathirvel
Lester Karen
Ravinarayanan Haribalaganesh
Ramasamy Krishnadas
Veerappan Muthukkaruppan
Brian Lane
David A. Simpson
Kasia Goljanek-Whysall
Carl Sheridan
Devarajan Bharanidharan
Colin E. Willoughby
Srinivasan Senthilkumari
author_sort Kandasamy Kathirvel
collection DOAJ
description Abstract In the quest of identifying newer molecular targets for the management of glucocorticoid-induced ocular hypertension (GC-OHT) and glaucoma (GCG), several microarray studies have attempted to investigate the genome-wide transcriptome profiling of primary human trabecular meshwork (TM) cells in response to dexamethasone (DEX). However, no studies are reported so far to demonstrate the temporal changes in the expression of genes in the cultured human TM cells in response to DEX treatment. Therefore, in the present study, the time-dependent changes in the genome-wide expression of genes in primary human TM cells after short (16 hours: 16 h) and long exposure (7 days: 7 d) of DEX was investigated using RNA sequencing. There were 199 (118 up-regulated; 81 down-regulated) and 525 (119 up-regulated; 406 down-regulated) DEGs in 16 h and 7 d treatment groups respectively. The unique genes identified in 16 h and 7 d treatment groups were 152 and 478 respectively. This study found a distinct gene signature and pathways between two treatment regimes. Longer exposure of DEX treatment showed a dys-regulation of Wnt and Rap1 signaling and so highlighted potential therapeutic targets for pharmacological management of GC-OHT/glaucoma.
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spelling doaj.art-45cf67c53c1f4538bc2c8bc176477bbb2022-12-22T03:25:54ZengNature PortfolioScientific Reports2045-23222022-05-0112111110.1038/s41598-022-12443-7Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitroKandasamy Kathirvel0Lester Karen1Ravinarayanan Haribalaganesh2Ramasamy Krishnadas3Veerappan Muthukkaruppan4Brian Lane5David A. Simpson6Kasia Goljanek-Whysall7Carl Sheridan8Devarajan Bharanidharan9Colin E. Willoughby10Srinivasan Senthilkumari11Department of Ocular Pharmacology, Aravind Medical Research FoundationGenomic Medicine, Biomedical Sciences Research Institute, Ulster UniversityDepartment of Ocular Pharmacology, Aravind Medical Research FoundationGlaucoma Clinic, Aravind Eye HospitalAravind Medical Research FoundationTranslational Radiobiology Group, Division of Cancer Sciences, Manchester Academic Health Science Centre, Christie NHS Foundation Trust Hospital, University of ManchesterSchool of Medicine, Dentistry and Biomedical Sciences, The Wellcome – Wolfson Institute for Experimental Medicine, Queen’s University BelfastSchool of Medicine, Physiology, National University of Ireland GalwayDepartment of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of LiverpoolDepartment of Bioinformatics, Aravind Medical Research FoundationGenomic Medicine, Biomedical Sciences Research Institute, Ulster UniversityDepartment of Ocular Pharmacology, Aravind Medical Research FoundationAbstract In the quest of identifying newer molecular targets for the management of glucocorticoid-induced ocular hypertension (GC-OHT) and glaucoma (GCG), several microarray studies have attempted to investigate the genome-wide transcriptome profiling of primary human trabecular meshwork (TM) cells in response to dexamethasone (DEX). However, no studies are reported so far to demonstrate the temporal changes in the expression of genes in the cultured human TM cells in response to DEX treatment. Therefore, in the present study, the time-dependent changes in the genome-wide expression of genes in primary human TM cells after short (16 hours: 16 h) and long exposure (7 days: 7 d) of DEX was investigated using RNA sequencing. There were 199 (118 up-regulated; 81 down-regulated) and 525 (119 up-regulated; 406 down-regulated) DEGs in 16 h and 7 d treatment groups respectively. The unique genes identified in 16 h and 7 d treatment groups were 152 and 478 respectively. This study found a distinct gene signature and pathways between two treatment regimes. Longer exposure of DEX treatment showed a dys-regulation of Wnt and Rap1 signaling and so highlighted potential therapeutic targets for pharmacological management of GC-OHT/glaucoma.https://doi.org/10.1038/s41598-022-12443-7
spellingShingle Kandasamy Kathirvel
Lester Karen
Ravinarayanan Haribalaganesh
Ramasamy Krishnadas
Veerappan Muthukkaruppan
Brian Lane
David A. Simpson
Kasia Goljanek-Whysall
Carl Sheridan
Devarajan Bharanidharan
Colin E. Willoughby
Srinivasan Senthilkumari
Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro
Scientific Reports
title Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro
title_full Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro
title_fullStr Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro
title_full_unstemmed Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro
title_short Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro
title_sort short and long term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro
url https://doi.org/10.1038/s41598-022-12443-7
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