Gene expression profile of human trabecular meshwork cells inresponse to long-term dexamethasone exposure

[摘要] Purpose: Topical use of dexamethasone has long been associated withsteroid induced-glaucoma, although the mechanism is unknown. We applieda strict filtering of comparative microarray data to more than 18,000genes to evaluate global gene expression of cultured human trabecularmeshwork cells in response to treatment with dexamethasone.Methods: Three human trabecular meshwork cell primary cultures fromnonglaucomatous donors were incubated with and without dexamethasone for21 days. Relative gene expression was evaluated by analysis of U133AGeneChip and the results validated using quantitative polymerase chainreaction (PCR).Results: Application of strict filtering to include only genes withstatistically significant differences in gene expression across allthree trabecular meshwork cell cultures produced a list of 1,260 genes.Significant changes in signal level were observed, including 23upregulated and 18 downregulated genes that changed greater than threefold in each of three cell cultures. Using quantitative PCR we foundchanges greater than a thousand fold for two genes (SLP1 and SAA2) andchanges greater than a hundred fold for another five genes (ANGPTL7,MYOC, SAA1, SERPINA3, and ZBTB16).Conclusions: Expression changes in trabecular meshwork cells inresponse to dexamethasone treatment indicate that a group of actins andactin-associated proteins are involved in the development ofcross-linked actin networks that form in response to dexamethasone. Atrend was identified toward decreased expression of protease genesaccompanied by an increased expression of protease inhibitors. Such atrend in nonproteasomal proteolysis conceivably affects gene productlevels above the level of transcription. Only two genes, MYOC andIGFBP2, showed significantly elevated expression after dexamethasonetreatment in our study and the other three previously published reportsof primary culture trabecular meshwork cell gene expression.

[学科分类] 生物化学/生物物理