Nitric oxide and lens-associated uveitis (LAU)


Conference Paper

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 Authors

Cited Authors

  • Aaberg, T; Rolon, A; Cousins, SW

Published Date

  • December 1, 1997

Published In

Volume / Issue

  • 38 / 4

International Standard Serial Number (ISSN)

  • 0146-0404

Citation Source

  • Scopus