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X. Zhao, R. Gerometa, J. Danias, O. Candia, T. Mittag, S. M. Podos; Gene Expression Changes in Steroid-Induced Ocular Hypertension in Cows. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2081.
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To determine whether gene expression changes occur in the trabecular meshwork of cow eyes in which steroid-induced intraocular pressure (IOP) elevation was produced.
Adult female Braford cows (N=8) were subjected to uniocular treatment with prednisolone acetate TID for a period of 6 weeks. IOP was monitored with a Perkins applanation tonometer calibrated using calibration curves derived from in vitro cannulation manometric experiments and validated with in vivo manometric measurement. At the conclusion of the experiment, animals were sacrificed, the eyes were enucleated and the trabecular meshwork was dissected out and stored in RNA-later. RNA was extracted and subjected to microarray analysis using Affymetrix oligonucleotide arrays. Some of the genes identified to be differentially expressed between control and experimental eyes were confirmed by RT-PCR.
IOP began to increase after three weeks of treatment in 100% of the cow eyes receiving corticosteroid and reached a peak one week later. IOP differences between the corticosteroid-treated eye and the fellow control eye were 6 + 2 mmHg (mean + SD) at the conclusion of the study. Microarray analysis revealed that expression of 163 genes was up-regulated while expression of 99 genes was downregulated in the trabecular meshwork of eyes with steroid-induced IOP elevation. Genes identified to be differentially expressed include genes coding for cytoskeletal proteins, enzymes, growth and transcription factors, as well as extracellular matrix proteins and immune response proteins.
Bovine eyes exhibit a robust steroid-induced ocular hypertensive response. This IOP elevation alters gene expression in the trabecular meshwork. Since the mechanism(s) of steroid-induced glaucoma may be related to those involved in primary open-angle glaucoma, this new animal model may provide clues to elucidate the pathogenesis of the latter.
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