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Y. Okada, S. Saika, T. Ueyama, K. Shirai, O. Yamanaka, Y. Ohnishi, P. S. Reinach; Effects of Topical Anti-Glaucoma Medications on Ocular Surface as Evaluated by Gene Expression Pattern. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4814.
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To examine the expression pattern of stress-related genes, c-fos and c-jun, both the major components of AP-1, and cyclooxygenase-2 (COX-2) in rat ocular surface treated with topical anti-glaucoma medications and benzalkonium chloride preservative.
Fifty-two male Wistar rats were used. Anti-glaucoma medications (0.5% timolol, 0.005% latanoprost or 0.12% unoprostone), chemical constituent or benzalkonium chloride preservative (0.005%, 0.01% or 0.02%) were topically applied on the one eye of each animal. The eyes were enucleated after various intervals. In situ hybridization and immunohistochemistry were employed to detect expression of c-fos, c-jun and COX-2.
Expression of c-fos, c-jun and COX-2 was minimally observed in an uninjured rat corneal epithelium. Thirty to 60 min after applying these all anti-glaucoma medications, signals for c-fos and c-jun mRNAs were detected in the corneal epithelium. Thirty to 60 min after applying 0.005% latanoprost or 0.12% unoprostone, but not timolol, signal for COX-2 were detected in corneal and conjunctival epithelium. Expression of c-fos and c-jun seemed more marked with prostaglandins as compared with timolol. Thirty to 60 min after dropping 0.02% benzalkonium chloride preservative, signals for c-fos and c-jun mRNAs were detected in the conjunctival epithelium. Signal for COX-2 was not induced by applying 0.5%timolol or benzalkonium chloride preservative. Signal for these mRNAs were not affected by applying 0.005% or 0.01% benzalkonium chloride preservative. Proteins of these components were also detected, indicating that each mRNA expression was followed by protein synthesis.
Corneal and conjunctival epithelial cells are transiently transcriptionally activated at a very early phase following topical administration of anti-glaucoma medications and benzalkonium chloride preservative. Stimulatory effects of prostaglandins on corneal epithelial cells seemed more marked as compared with timolol. Expression of COX-2 may potentially involve in inflammatory response in corneal epithelium.
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