May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Gene Expression Changes in Rat Aqueous Outflow Tissues With Intracameral Kenalog (Triamcinolone Acetonide)
Author Affiliations & Notes
  • M. R. Castro-Paiz
    Biological Sciences, Allergan, Inc, Irvine, California
  • J. L. Edelman
    Biological Sciences, Allergan, Inc, Irvine, California
  • Footnotes
    Commercial Relationships  M.R. Castro-Paiz, Allergan, Inc., E; J.L. Edelman, Allergan, Inc., E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1655. doi:
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    • Get Citation

      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.

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: gene microarray • outflow: trabecular meshwork • corticosteroids 
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