Abstract
Purpose: :
To investigate the effect of inducible nitric oxide synthases (iNOS) on inflammatory reactions during endotoxin-induced uveitis (EIU) in mice by studying leukocyte-endothelial cell interactions.
Methods: :
EIU was produced in immunosuppressed (IS) iNOS-/- mice and C57BL/6 (normal) mice by footpad injection of lipopolysaccharide (LPS). Leukocytes were labeled with acridine orange. Leukocyte rolling in the retinal microcirculation was evaluated in vivo with acridine orange digital fluorography. The number of migrated leukocytes was counted in flatmounted retina.
Results: :
Both leukocyte rolling and migration peaked at 48 hours after LPS injection. The maximal numbers of rolling leukocytes in the IS iNOS-/- mouse retina decreased by 98.2% (p<0.0001) as compared with that in the normal mouse retina at 48 hours after LPS injection. In addition, the maximal numbers of migrated leukocytes in the IS iNOS-/- mouse retina decreased by 74.0% (p<0.0001) as compared with that in the normal mouse retina at 24 hours after LPS injection. Furthermore, the diameters of major retinal veins of the IS iNOS-/- group were smaller at both 24 and 48 hours after LPS injection than were those of the normal group (p<0.0001, respectively).
Conclusions: :
A lack of iNOS suppresses leukocyte-endothelial cell interactions in retinas of mice with EIU. This suggests that iNOS may have a role in the management of patients with uveitis and other inflammatory conditions.
Keywords: retina • inflammation • nitric oxide