Abstract
Purpose::
Corticosteroids such as triamcinolone acetonide (TA) and dexamethasone (DEX) are one of the most potent and effective modalities available in the treatment of ocular inflammation. Both TA and DEX can cause elevation of intraocular pressure and lead to steroid-induced glaucoma. Therefore, investigation of the gene expression profile of human trabecular meshwork (hTM) cells in common between TA and DEX should be helpful to elucidate whether different corticosteroids share similar mechanisms in their inducing ocular hypertension and glaucoma. The purpose of this study is to investigate the differential gene expression profile of hTM cells in response to TA and to identify commonly expressed genes between TA and DEX treated hTM cells.
Methods::
Total RNA was extracted from cultured hTM cells treated with TA or DEX and used for a gene microarray expression analysis. The microarray experiments were repeated three times. Differentially expressed genes were identified by an empirical Bayes approach and confirmed by real-time quantitative PCR.
Results::
0.1 mg/ml TA treatment resulted in 15 genes up-regulated and 10 genes down-regulated while 1mg/ml TA treatment resulted in 34 genes up-regulated and 20 genes down-regulated. These genes were mainly associated with acute-phase response, cell adhesion, cell cycle and growth, growth factor, ion binding, metabolism, proteolysis and transcription factor. Five genes were commonly differentially expressed in both TA and DEX treatment, including MYOC, GAS1, SENP1, ZNF343 and SOX30. Eight differentially expressed genes were located in the known glaucoma loci, including MYOC, SOAT1, CYP27A1, SPOCK, SEMA6A, EGR1, GAS1 and ATP10A. Majority of them were located in juvenile-onset primary open-angle glaucoma loci.
Conclusions::
Microarray technology was used to show, for the first time, that the TA treated hTM cells have a different gene expression profile between different concentrations of TA treatment. TA and DEX treatment shared several differentially expressed genes, indicating the same pathways to cause ocular hypertension and glaucoma.
Keywords: gene microarray • trabecular meshwork • intraocular pressure