Expression of cell adhesion molecules on limbal and neovascular endothelium in corneal inflammatory neovascularization

Abstract

PURPOSE: To investigate the expression of cell-adhesion molecules on corneolimbal and neovascular endothelium and the associated leukocyte infiltration in an experimental model of inflammatory corneal neovascularization (NV). METHODS: Corneal NV was induced in BALB/c mice by placement of nylon sutures. Interleukin-1 receptor antagonist (IL-1ra) was used topically to determine whether suppression of IL-1 could affect adhesion molecule expression and leukocytic infiltration. At set time points, corneal samples were analyzed immunohistochemically for expression of P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, and platelet- endothelial adhesion molecule (PECAM)-1. Leukocytic infiltration at different time points was quantified histologically. In companion experiments mice deficient in ICAM-1 were investigated to determine the functional relevance of this molecule in corneal leukocyte infiltration. RESULTS: Significant enhanced expression of ICAM-1 was detected on the corneolimbal vascular endothelium as early as 8 hours and on the newly formed corneal NV by day 3, and treatment with IL-1ra led to significant suppression of this expression. IL-1ra-induced suppression of ICAM-1 expression was accompanied by a profound decrease in corneal leukocytic infiltration by 44.6% at day 1 (P < 0.003), 71.8% at day 3 (P < 0.001), 60.1% at day 7 (P < 0.001), and 63.8% at day 14 (P < 0.001), compared with control corneas. Similarly, in ICAM-1 knockout mice, the corneal leukocytic infiltration was 50.3%, 52.9%, and 36.4%, compared with wild-type control animals on day 1 (P < 0.001), day 7 (P < 0.005), and day 14 (P < 0.001), respectively. Expression of PECAM-1 was constitutively present on perilimbal vascular endothelium and had no response to IL-1ra treatment. No significant expression of P-selectin, E-selectin, or VCAM-1 was detected in this experimental model. CONCLUSIONS: These results suggest that leukocytic infiltration in this model of inflammatory corneal NV is closely associated with ICAM-1 expression, and that topical IL-1ra displays corneal anti-inflammatory effects, largely by suppressing ICAM-1 expression on vascular endothelial cells.