Nitric oxide and lens-associated uveitis (LAU)

Purpose: To evaluate the role of nitric oxide (NO) as a macrophage-derived inflammatory mediator in LAU. We have developed a model that requires AC injection of P. acnes antigens at the time of lens capsule injury in a previously immunized mouse. Intraocular T cell activation (i.e., delayed hypersensitivity) results in local production of interferon-gamma (IFN-y) which, in turn, activates intraocular macrophages. We hypothesize that activated macrophages nonspecifically induce LAU via mediators such as NO. Methods: A series of experiments was performed to evaluate the capacity of IFN-γ plus P. acnes to induce NO production by macrophages in vitro and in vivo. Also, we evaluated the efficacy of a nitric oxide synthase inhibitor, L-NMMA, on macrophage-derived NO production in vitro and in two different LAU models in vivo. Results: As expected, iri vitro incubation of macrophages with IFN-γ plus P.acnes antigen was effective in activating NO production, which was blocked by 75% after incubation with 500 uM L-NMMA. Also, medium conditioned by murine iris/ciliary body expiants harvested from eyes inoculated with IFN-y plus P.acnes produced more than a four-fold increase in NO release compared to saline-injected controls. Nevertheless, eyes from mice treated daily with 5 mg L-NMMA demonstrated minimal reduction of LAU frequency or severity. Additionally, mice with LAU induced by AC transfer of activated macrophages pre-treated with 500 uM L-NMMA also failed to demonstrate any significant reduction of inflammation compared to LAU induced by macrophages treated with saline. Conclusion: NO production within ocular tissue, presumably by activated macrophages, is detectable during LAU. However, it remains unclear if NO is crucial in mediating inflammation in this model.

Duke Scholars

Author Scott William Cousins Ophthalmology, Vitreoretinal Diseases & Surgery