Delayed onset and decreased severity of experimental autoimmune uveoretinitis in mice lacking nitric oxide synthase type 2

Abstract

To investigate the role of nitric oxide (NO), produced by the inducible form of NO synthase (NOS-2) in the development of experimental autoimmune uveoretinitis (EAU), we immunized C57BL/6×129Sv (H-2 b) mice carrying a targeted disruption of the gene encoding NOS-2 (NOS-2[−/−]), and wild-type (WT) C57BL/6×129Sv controls with interphotoreceptor retinoid binding protein (IRBP). NOS-2[−/−] mice developed a clinical EAU with delayed onset and decreased severity compared to WT controls. The ocular tissues from WT mice contained activated F4/80 macrophages with NOS-2 expression and retinal destruction whereas less intense EAU was detected in NOS-2[−/−] mice. The expression of NOS-2 mRNA was detected in the retina at the peak of EAU in WT. Analysis of cytokine production in the spleen from NOS-2[−/−] mice by RT-PCR showed high levels of IL-10 mRNA. Our results demonstrate that NO is clearly involved in EAU and may be important for the regulation of immune responses through the regulation of IL-10.