AP–1 and COX–2 Expression in Corneal Epithelium Following Anti–Glaucomatous Eyedrops

Abstract

Abstract: : Purpose: 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 corneal epithelium treated with anti–glaucomatous eyedrops. Methods: Seventy–six male Wistar rats were used. We dropped anti–glaucomatous eyedrops (0.5%timolol, 0.005%latanoprost or 0.12%unoprostone) on the one eye of rat. The affected eyes were enucleated after various intervals. Frozen sections were processed for in situ hybridization with c–fos, c–jun and COX–2 mRNAs or were stained with anti–c–Fos and anti–COX–2 antibodies. Results: Thirty min after dropping 0.5%timolol, signals for c–fos and c–jun mRNAs were detected in the corneal epithelium. Thirty to 60 min after dropping 0.005%latanoprost or 0.12%unoprostone, signals for c–fos and c–jun mRNAs were detected in the corneal epithelium. Thirty to 90 min after dropping 0.005%latanoprost or 0.12%unoprostone, signals for COX–2 mRNA was detected in the corneal epithelium. These signals were no longer evident at 120 min. c–Fos protein was detected in the corneal epithelium 120 min after dropping 0.5%timolol, 0.005%latanoprost or 0.12%unoprostone. COX–2 protein was detected in the corneal epithelium 120 min after dropping 0.005%latanoprost or 0.12%unoprostone. Conclusions: Corneal epithelial cells are transiently transcriptionally activated at a very early phase following anti–glaucomatous eyedrops. Expression of COX–2 following these eyedrops may potentially induce inflammatory response in cornea.

Keywords: drug toxicity/drug effects • cornea: epithelium • in situ hybridization