Abstract
Abstract: :
Purpose: There are two known isoforms of cyclooxygenase (COX): COX-1 is relatively ubiquitously and constitutively expressed, whereas COX-2 has been shown to be robustly induced in various acute, inflammatory-induced pathologies. COX-2 has been detected in sites of inflammation related to a variety of immune and ulcerative diseases, and COX-2 derived eicosanoids have been implicated in local tissue destruction. Despite the plethora of reports on COX-2 in systemic inflammation, its expression has not been characterized in the normal cornea or inflammatory corneal pathologies. Methods: Appropriate IRB approval was obtained to examine corneal buttons from keratoplasty patients exhibiting both acute and resolved inflammation. All specimens were embedded in paraffin and originated from the University of Illinois-Chicago Eye Center. The six specimens included acute fungal infection (2), autoimmune keratolysis (2), alkali burn with keratolysis (1), and quiescent interstitial keratitis with stromal neovascularization (1). COX-2 expression and distribution was analyzed by immunohistochemical (IHC) analysis in all specimens. Normal human kidneys were utilized as positive controls, and COX-2 was expressed as expected. No appreciable staining was observed in isotype matched-IgG controls. All specimens were read by a licensed pathologist (NK). Results: COX-2 was not detected in normal human corneas. In contrast, COX-2 was strongly expressed in the stroma and epithelium in patients with acute corneal inflammation. COX-2 immunoreactivity in the stroma and epithelium was further detected in ≷80% of patients with clinical keratolysis. Interestingly, COX-2 was not expressed in a patient with post-acute, clinically quiescent interstitial keratitis with chronic, stable neovascularization. Conclusion: In summary, COX-2 is not detected in normal human corneas, or in chronic corneal vascular structures induced by previous inflammation. In contrast, COX-2 is markedly upregulated in acute inflammatory pathologies of the cornea. Importantly, these observations imply COX-2 may play a role in acute inflammatory states in the eye, and may play a role in corneal inflammation associated with clinical necrosis and keratolysis. These data further suggest exploration of the clinical utility of COX-2 to treat acute corneal inflammation may be warranted.
Keywords: 370 cornea: basic science • 437 inflammation • 507 pathology: human