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Marlyn P Langford, Thomas B Redens, Chanping Liang, Marcy Landry, A. Scott Kavanaugh, William A Byrd; Conjunctivitis and anterior uveitis induced by topical application of Nod1 ligand in rabbits.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5781.
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NOD1 (nucleotide-oligomerization domain; an intracellular pattern-recognition molecule) senses peptidoglycan (PGN) fragments containing meso-diaminopimelic acid (DAP) present in Gram-negative bacilli and particular Gram-positive bacteria. We investigated the pro-inflammatory effect of topical application of the bacterial cell wall NOD1 ligand in rabbits.
C12-iE-DAP (50 µg/100 µl, acylated derivative of iE-DAP; γ-D-Glu-mDAP) or the NOD1 control γ-D-Glu-Lys (50 µg/100 µl, iE-Lys, a dipeptide present in the PGN of Gram-positive bacteria, but is not recognized by NOD1) was applied to the surface of one eye of New Zealand white rabbits (1.5-2 kg). The inflammatory changes were assessed by ocular examinations, tear production, 72 h aqueous humor (AH), serial tear and serum protein levels, electrophoretic protein profiles and/or γ-glutamyl transpeptidase (γ-GT, marker of PMN inflammation) activity.
Bilateral anterior ocular inflammation characterized by conjunctivitis and anterior uveitis/iritis with aqueous flare was detected by 4 h post injection of C12-iE-DAP, but not in rabbits receiving topical iE-Lys. Concomitantly, bilateral tear production, tear proteins and γ-GT levels increased 2 to 10-fold through 12-16 h in C12-iE-DAP rabbits, more so in the ipsilateral eye. AH protein levels were higher in the ipsilateral eyes that received the NOD1 ligand than the contralateral eyes and the AH protein levels were lower in the AH of bilateral iE-Lys treated eyes. The anterior uveitis persisted through 72 h.
While topical application of bacterial PGN and lipopolysaccharide have not been reported to induced ocular inflammation, topical application of the NOD1 ligand (C12-iE-DAP) induced ocular inflammation in rabbits that was very similar to that induced by topical muramyl dipeptide (NOD2 ligand). Thus, NOD1 ligands generated during bacterial colonization of the ocular surface may also induce conjunctival and uveal inflammation.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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