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WR Lo, EC Porterfield, P Yang, MR Hernández, T Borrás; Microarray Comparison Of Genes Induced By Dexamethasone (DEX) In The Human Trabecular Meshwork And Astrocytes . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1052.
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Purpose: Genes induced by DEX in the human trabecular meshwork (HTM) and not in other tissues might be relevant for the regulation of TIGR/MYOC and/or implicated in the development of steroid glaucoma. Our goal is to search for those genes specifically induced by DEX in the HTM. Methods: Three primary cell lines (2 HTM and 1 optic nerve head (ONH) astrocytes) were derived from three different individuals with no history of glaucoma. Early passages of confluent cells were treated with 100 nM DEX for 7 days. Samples were processed from total RNA to fragmented cRNA, labeled and hybridized onto Affymetrix U95Av2 GeneChips (n=6) at the Duke University microarray facility. Four paired comparisons of DEX-astrocytes (baseline) vs. DEX-HTM (experimental) and one comparison of astrocytes (baseline) vs. HTM (experimental) were analyzed using the Affymetrix GeneChip software. This program normalizes expression values against internal controls and eliminates genes absent in both chips from the comparisons. The twelve genes with the highest fold change values in each of the four DEX comparisons were screened against tissue specific genes. From this set, genes with fold-change values ≤5 in two comparisons were removed. The resulting genes were designated "most induced TM DEX specific genes." Results: In one of the four DEX comparisons, fourteen percent of the 12,629 genes on the chip were significantly up- or down-regulated by DEX in the HTM and, of those, 492 (3.9%) were up-regulated (249 of them with a fold change ≥4). To date, in addition to TIGR/MYOC, fourteen of the 249 genes were located in chromosomal regions linked to glaucoma. A total of eleven genes met the criteria for most induced TM DEX specific genes. These include, in addition to TIGR/MYOC: two serine protease inhibitors, two potent anti-angiogenic factors, two genes involved in ECM remodeling, one smooth muscle actin gene and one gene each involved in lipid transport, prostaglandin synthesis, nitric oxide metabolism and mitochondrial membrane transport. Conclusions: Genes specifically induced by DEX in the HTM vs. ONH astrocytes reveal the presence of both protective and damaging mechanisms for maintenance of physiologic IOP. In addition to TIGR/MYOC, other TM DEX specific genes might be good candidates for linkage to glaucoma.
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