Genome-Wide RNA Sequencing of Human Trabecular Meshwork Cells Treated with TGF-β1: Relevance to Pseudoexfoliation Glaucoma
Anton W. Roodnat,
Breedge Callaghan,
Chelsey Doyle,
Megan Henry,
Katarzyna Goljanek-Whysall,
David A. Simpson,
Carl Sheridan,
Sarah D. Atkinson,
Colin E. Willoughby
Affiliations
Anton W. Roodnat
Genomic Medicine, Biomedical Sciences Research Institute, Ulster University, Coleraine Campus, Coleraine BT52 1SA, Northern Ireland, UK
Breedge Callaghan
Genomic Medicine, Biomedical Sciences Research Institute, Ulster University, Coleraine Campus, Coleraine BT52 1SA, Northern Ireland, UK
Chelsey Doyle
Genomic Medicine, Biomedical Sciences Research Institute, Ulster University, Coleraine Campus, Coleraine BT52 1SA, Northern Ireland, UK
Megan Henry
Genomic Medicine, Biomedical Sciences Research Institute, Ulster University, Coleraine Campus, Coleraine BT52 1SA, Northern Ireland, UK
Katarzyna Goljanek-Whysall
School of Medicine, Physiology, National University of Ireland Galway, H91 W5P7 Galway, Ireland
David A. Simpson
The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University, Belfast BT9 7BL, Northern Ireland, UK
Carl Sheridan
Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, England, UK
Sarah D. Atkinson
Personalised Medicine Centre, Ulster University, Londonderry BT47 6SB, Northern Ireland, UK
Colin E. Willoughby
Genomic Medicine, Biomedical Sciences Research Institute, Ulster University, Coleraine Campus, Coleraine BT52 1SA, Northern Ireland, UK
Pseudoexfoliation glaucoma (XFG) is an aggressive form of secondary open angle glaucoma, characterised by the production of exfoliation material and is estimated to affect 30 million people worldwide. Activation of the TGF-β pathway by TGF-β1 has been implicated in the pathogenesis of pseudoexfoliation glaucoma. To further investigate the role of TGF-β1 in glaucomatous changes in the trabecular meshwork (TM), we used RNA-Seq to determine TGF-β1 induced changes in the transcriptome of normal human trabecular meshwork (HTM) cells. The main purpose of this study was to perform a hypothesis-independent RNA sequencing analysis to investigate genome-wide alterations in the transcriptome of normal HTMs stimulated with TGF-β1 and investigate possible pathophysiological mechanisms driving XFG. Our results identified multiple differentially expressed genes including several genes known to be present in exfoliation material. Significantly altered pathways, biological processes and molecular functions included extracellular matrix remodelling, Hippo and Wnt pathways, the unfolded protein response, oxidative stress, and the antioxidant system. This cellular model of pseudoexfoliation glaucoma can provide insight into disease pathogenesis and support the development of novel therapeutic interventions.
