Gene expression profiles of human trabecular meshwork cells induced by triamcinolone and dexamethasone.
OBJECTIVE
Triamcinolone acetonide (TA) and dexamethasone (DEX) are corticosteroids commonly used for ocular inflammation, but both can cause ocular hypertension. In this study, the differential gene expression profile of human trabecular meshwork (TM) cells in response to treatment by TA in comparison with DEX was investigated.


METHODS
Total RNA was extracted from cultured human TM cells treated with TA or DEX and used for microarray gene expression analysis. The microarray experiments were repeated three times. Differentially expressed genes were identified by an empiric Bayes approach and confirmed by real-time quantitative PCR.


RESULTS
TA (0.1 mg/mL) treatment resulted in 15 genes upregulated and 12 genes downregulated, whereas 1 mg/mL TA resulted in 36 genes upregulated and 21 genes downregulated. These genes were mainly associated with acute-phase response, cell adhesion, cell cycle and growth, growth factor, ion binding, metabolism, proteolysis and transcription factor. Two genes, MYOC and GAS1, were upregulated, and three genes, SENP1, ZNF343, and SOX30, were downregulated by both TA and DEX treatment. Eight differentially expressed genes were located in known primary open-angle glaucoma (POAG) loci, including MYOC, SOAT1, CYP27A1, SPOCK, SEMA6A, EGR1, GAS1, and ATP10A.


CONCLUSIONS
Differential gene expression profiles of human TM cells treated by TA and DEX, and a dosage effect by TA, were revealed by microarray technology. TA and DEX treatment shared several differentially expressed genes, suggesting a common mechanism to cause ocular hypertension. Some differentially expressed genes located in the known POAG loci are potential candidates for glaucoma genes.
Fan
Bao Jian
BJ
Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong, China.
Wang
Dan Yi
DY
Tham
Clement Chee Yung
CC
Lam
Dennis Shun Chiu
DS
Pang
Chi Pui
CP
D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D005136:Eye Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005902:Glaucoma, Open-Angle / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014129:Trabecular Meshwork / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000494:pharmacology*
D005136:Eye Proteins; D005938:Glucocorticoids; D012333:RNA, Messenger; D003907:Dexamethasone; D014222:Triamcinolone Acetonide