TOPICAL MODULATION OF INTERLEUKIN-1 ACTIVITY IN CORNEAL NEOVASCULARIZATION

Purpose. To determine whether inflammatory corneal neovascularization (CNV) is associated with interleukin-1 (IL-1) activity and if so, to a ssess the efficacy of topical interleukin-l receptor antagonist (IL-1r a) to suppress CNV. Methods. Inflammatory CNV was induced on day 0 by placement of paracentral intrastromal sutures in BALB/c murine eyes. Q uantification of IL-1 alpha and -beta cytokine levels was done by a sa ndwich enzyme-linked immunosorbent assay (ELISA) on the supernatants o f incubated corneas excised at specified time points after induction o f CNV (n = 6 per time point studied). To study suppression of CNV by I L-1ra, animals were divided into treat ment subgroups that received to pical 20 mg/ml of IL-1ra mixed in 0.2% sodium hyaluronate (n = 28) or placebo (vehicle), alone (n = 22) 3 times daily during days 0-35. Othe r groups of animals received placebo for 1 (n = 10) or 2 (a = 14) week s before being switched and retained on IL-1ra. Neovascularization was assessed biomicroscopically and graded by using a standardized scheme . Results. Induction of CNV stimulus was associated with a significant surge in the expression of both IL-1 alpha (p < 0.001) and IL-1 beta (p < 0.001) as early as 2 h after the stimulus, which peaked at 24 h, before decreasing substantially in the case of IL-IP and returning to basal levels by day 7. Topical application of IL-1ra led to a signific ant suppression of CNV for the duration of therapy only if initiated e arly after induction of the neovascular stimulus. Initiation of therap y 1 week after CNV induction was associated only with a transient supp ression in the angiogenic response. Conclusion. Our data strongly impl icate IL-1 as a critical mediator in the early phase of CNV and sugges t that IL-1ra can be an effective modality in suppressing CNV if initi ated sufficiently early after the inflammatory neovascular stimulus.