Abstract
Abstract: :
Purpose:To determine cyclooxygenase (COX) isoenzyme expression in a traumatized rat cornea model and the effect of selective topical cyclooxygenase–1 (COX–1) and cyclooxygenase–2 (COX–2) inhibition. Methods:Sprague–Dawley rats (n=28) were anesthetized, prepped and given topical proparacaine and ofloxacin. The right eye of each animal was traumatized with a pass of 2.75mm corneal keratome or the placement of an 8–0 braided silk suture partial– thickness in the peripheral cornea. Rats were randomized to receive a water–insoluble COX–1 inhibitor (506, Pharmacia) in 100% DMSO, a water–soluble COX–2 inhibitor (Paracoxib 0.03%, Pharmacia), 100% DMSO (as a control for COX–1 inhibition), and no treatment. All rats received ofloxacin for 1 week post–operatively. Serial photography was performed. 8 rats, two per treatment group, were sacrificed at each Day 2, Week 1, and Week 3 time point and globes placed in formalin. Sections of whole globes were immunolabeled with polyclonal COX–1 (Cayman, 160109) and COX–2 (Cayman, 160126) antibodies using indirect immunohistochemistry. The immunoreactivity (IR) was assessed semiquantitatively by a masked observer. Results:Clinical examination of the eyes showed subjectively more inflammation in eyes treated with the COX–1 inhibitor compared to other treatment groups. Traumatized eyes showed increased anti COX–1 IR on Day 2 and Week 1and anti COX–2 IR on Day 2 in the areas of trauma vs. normal cornea. On Day 2, COX–1 inhibition resulted in increased (2+) anti COX–2 IR in the keratocytes in wounded corneal stroma, associated inflammatory cells and adjacent conjunctiva vs. controls (1+). COX–1 inhibition resulted in anterior chamber inflammation not seen in DMSO controls or other treatment groups. COX–1 inhibition had little effect on anti COX–1 IR on Day 2, but showed suppression in Week 1(trace–1+) vs. controls (2+). On Day 2, COX–2 inhibited rats showed decreased levels of corneal wound expression of COX–2 (0–0.5+) vs. controls (1–1.5+). COX–2 staining was minimal at other time points. Conclusions:Systemically, COX–1 and COX–2 have different roles in acute inflammation, homeostatic and degradative, respectively. In the rat, COX–1 and COX–2 appear to be similarly expressed in acute trauma and inflammation, not found in the normal state. Topical COX–1 and COX–2 inhibitors appear to have a distinguishable and differential clinical effect on COX isoenzyme expression probably through promotion or suppression of inflammation, respectively. This may have implications in the use of selective COX inhibitors in humans to limit inflammation and resulting tissue damage.
Keywords: enzymes/enzyme inhibitors • cornea: stroma and keratocytes • inflammation