Abstract
Purpose :
Intraocular pressure elevation is commonly observed in patients and rabbits with uveitis. Hyperlipidemia (milky serum) is associated with endotoxemia. We investigated the intraocular and systemic effects of intravenous injection of the bacterial cell wall endotoxin NOD1 (nucleotide-oligomerization domain 1; an intracellular pattern-recognition molecule) ligand in rabbits.
Methods :
NOD1 ligand, C12-iE-diaminopimelic acid (DAP) (50µg/100ul, acylated derivative of iE-DAP; γ-D-Glu-mDAP) or the NOD1 control ligand γ-D-Glu-Lys [(50µg/100ul), iE-Lys, a dipeptide present in the peptidoglycan of gram-positive bacteria, but is not recognized by NOD1] was injected (0.75-1.0 mg/kg) intravenously into 1.5-2 kg New Zealand white rabbits. Intraocular inflammatory changes were assessed by ocular examinations, TonopenTM intraocular pressure (IOP) measurement, aqueous humor (AH) protein and triglyceride levels, and aqueous humor and serum gamma-glutamyl transpeptidase (GGT) and triglyceride levels. Serum cell-free DNA electrophoretic profiles and levels were detected by gel electrophoresis.
Results :
Bilateral anterior ocular inflammation, characterized by anterior uveitis/iritis with aqueous flare and a 30% increased IOP (13.2±4.0 mm Hg; p<0.01), was detected by 4 hour post injection of C12-iE-DAP, but not in rabbits receiving iE-Lys. Concomitantly, AH proteins and GGT increased up to 10-fold, AH triglyceride increased 3-fold, and serum triglycerides increased 20-fold in C12-iE-DAP, but not iE-Lys, injected rabbits 12 to 72 hours post injection.
Conclusions :
The anterior uveitis was associated temporally with increased IOP, milky serum, and increased triglycerides and protein in the aqueous humor. The results suggest that degradation of bacterial cell wall by leukocytes during natural infection generates NOD1 ligands that can induce uveal inflammation with increased IOP and triglyceride.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.