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Gene expression profiles of human trabecular meshwork cells induced by triamcinolone and dexamethasone.

AbstractPURPOSE:
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.
AuthorsBao Jian Fan, Dan Yi Wang, Clement Chee Yung Tham, Dennis Shun Chiu Lam, Chi Pui Pang
JournalInvestigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 49 Issue 5 Pg. 1886-97 (May 2008) ISSN: 0146-0404 [Print] United States
PMID18436822 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Eye Proteins
  • Glucocorticoids
  • RNA, Messenger
  • Dexamethasone
  • Triamcinolone Acetonide
Topics
  • Cells, Cultured
  • Dexamethasone (pharmacology)
  • Eye Proteins (genetics)
  • Gene Expression Profiling
  • Gene Expression Regulation (drug effects)
  • Glaucoma, Open-Angle (genetics)
  • Glucocorticoids (pharmacology)
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger (metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trabecular Meshwork (metabolism)
  • Triamcinolone Acetonide (pharmacology)

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