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M. R. Castro-Paiz, J. L. Edelman; Gene Expression Changes in Rat Aqueous Outflow Tissues With Intracameral Kenalog (Triamcinolone Acetonide). Invest. Ophthalmol. Vis. Sci. 2008;49(13):1655. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Steroid-induced ocular hypertension (OHT) can be a common and sometimes use-limiting side effect of corticosteroid treatment. Little is known about the biological mechanisms that specifically mediate its development, and no small animal model of steroid-induced OHT is available to research it. The goal of the current study was to develop a surrogate model in rat with steroid injected directly into the anterior chamber for maximal exposure to the aqueous outflow pathway (e.g. trabecular meshwork), and to analyze early steroid-induced gene expression changes in these relevant tissues to identify biological processes that precede and possibly cause steroid-induced OHT.
Kenalog-40 (200 µg triamcinolone acetonide) or saline (control; 5 µl per injection) was injected intracamerally into both eyes of Wistar rats, and a third group of rats received no injection. Rats were sacrificed after 24 hours, and eyes (n=4 per treatment group) were enucleated and dissected to isolate the aqueous outflow tissues, which were then flash-frozen for RNA extraction. Whole rat genome microarray analysis was performed by Genus Biosystems using Agilent Array Technology.
Analysis of the 41,000+ genes in the rat genome detected 30,445 genes expressed above background in at least 3 of the 12 aqueous outflow tissue samples analyzed in this study. Of these genes, 3.7% (1,136 genes) are differentially expressed (>2-fold up or down; p<0.05) 24 hours after intracameral Kenalog in comparison to saline control. In Kenalog-treated tissues, the magnitude of upregulation is as high as 107-fold, and downregulation is as low as 0.02-fold; and more genes are significantly downregulated (688) than are upregulated (429). These genes represent multiple biological functions and pathways, including known glucocorticoid receptor responses, inflammation-associated processes that involve various cytokines and other mediators, and extracellular matrix proteins and enzymes.
This is the first report of whole transcriptome analysis of aqueous outflow tissues 24 hours after corticosteroid exposure in vivo. As a surrogate model for early development of steroid-induced OHT, its data on early gene expression changes in the relevant tissues provide insight into biological processes that precede and may cause this side effect.
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