PURPOSE: NOD1 plays an important role in host defense and recognizes the minimal 
component of bacterial cell walls, meso-diaminopimelic acid (iE-DAP). 
Polymorphisms in NOD1 are associated with autoinflammatory diseases 
characterized by uveitis such as Crohn's disease and sarcoidosis. NOD1 is 
homologous to NOD2, which is responsible for an autosomal dominant form of 
uveitis. Nonetheless, the role of NOD1 in intraocular inflammation has not been 
explored. The induction of uveitis by iE-DAP in mice and the potential 
contribution of interleukin (IL)-1beta were investigated.
METHODS: BALB/c mice or mice deficient in caspase-1 or IL-1R1 and their congenic 
controls were injected intravitreally with iE-DAP or saline. The time course, 
dose response, and contribution of IL-1beta to ocular inflammation were 
quantified by intravital video microscopy, histology, and immunohistochemistry. 
NOD1 and IL-1beta were measured in eye tissue by immunoblotting and ELISA.
RESULTS: NOD1 protein is expressed in the eye and promotes ocular inflammation 
in a dose- and time-dependent fashion. The authors previously defined the role 
of IL-1beta in NOD2 uveitis and tested whether NOD1 and NOD2 used similar 
mechanisms. Treatment with iE-DAP significantly increased IL-1beta, which was 
caspase-1 dependent. However, in contrast to NOD2, caspase-1 and IL-1R1 were 
essential mediators of iE-DAP-induced uveitis, suggesting that NOD1 and NOD2 
induce ocular inflammation by distinct mechanisms involving IL-1beta.
CONCLUSIONS: These findings demonstrate that NOD1 is expressed within the eye 
and that its activation results in uveitis in an IL-1beta-dependent mechanism. 
Characterizing the differences between NOD1 and NOD2 responses may provide 
insight into the pathogenesis of uveitis.