A Comparative Genome-Wide Transcriptome Analysis of Glucocorticoid Responder and Non-Responder Primary Human Trabecular Meshwork Cells

Genes

Devarajan Bharanidharan¹  Veerappan Muthukkaruppan²  Srinivasan Senthilkumari³  Kandasamy Kathirvel³  Ravinarayanan Haribalaganesh³  Colin E. Willoughby⁴  Ramasamy Krishnadas⁵ 

[1] Department of Bioinformatics, Aravind Medical Research Foundation, Madurai 625020, Tamilnadu, India;Department of Immunology and Stem Cell Biology, Aravind Medical Research Foundation, Madurai 625020, Tamilnadu, India;Department of Ocular Pharmacology, Aravind Medical Research Foundation, Madurai 625020, Tamilnadu, India;Genomic Medicine, Biomedical Sciences Research Institute, Ulster University, Newtownabbey BT37 0QB, UK;Glaucoma Clinic, Aravind Eye Hospital, Madurai 625020, Tamilnadu, India;

关键词: glucocorticoid-induced ocular hypertension;    human perfusion-cultured anterior segment;    trabecular meshwork cells;    gene expression;    RNA-seq;    candidate genes;   

DOI  :  10.3390/genes13050882

来源: DOAJ

【 摘 要 】

Aim: To investigate genes and pathways involved in differential glucocorticoid (GC) responsiveness in human trabecular meshwork (HTM) cells using RNA sequencing. Methods: Using paired human donor eyes, human organ-cultured anterior segment (HOCAS) was established in one eye to characterize GC responsiveness based on intra ocular pressure (IOP) change and, in the other eye, primary HTM cell culture was established. For RNA sequencing, total RNA extracted from GC-responder (GC-R) and non-responder (GC-NR) cells after dexamethasone (DEX) or ethanol (ETH) treatment for 7d was used. Differentially expressed genes (DEGs) were compared among five groups and validated. Results: In total, 616 and 216 genes were identified as significantly dysregulated in Group #1 and #2 (#1: ETH vs. DEX-treated GC-R; #2: ETH vs. DEX-treated GC-NR), respectively. Around 80 genes were commonly dysregulated in Group #3 (overlapping DEGs between #1 and #2), whereas 536 and 136 genes were uniquely expressed in GC-R (#4) and GC-NR HTM (#5) cells, respectively. Pathway analysis revealed that WNT signaling, drug metabolism cytochrome p450, cell adhesion, TGF-β signaling, and MAPK signaling were associated with GC responsiveness. Conclusion: This is the first study reporting distinct gene signatures and their associated pathways for GC-R and GC-NR HTM cells. WNT and MAPK signaling are potential therapeutic targets for the management of GC-induced glaucoma.

【 授权许可】

Unknown