Role of Platelet Activating Factor in LPS-induced Uveitis

Abstract

Purpose: : Uveitis is a common inflammatory disease, characterized by leukocyte infiltration in ocular tissues including retina. To investigate the possible role of the pro-inflammatory phospholipid, platelet activating factor (PAF), in this disease, we used the PAF inhibitor, Ginkgolide B (GB), in experimental uveitis.

Methods: : To induce uveitis, footpads of Lewis rats were injected with 100µg lipopolysaccharide (LPS), with or without GB pre-treatment. After 24 hrs, the animals were sacrificed and retinal flat mounts were prepared. In some rats, recombinant PSGL-1 conjugated fluorescent microspheres were injected systemically 3 hrs before sacrifice to perform in vivo imaging. The number of firmly adhering leukocytes and microspheres in retinal vessels were counted.

Results: : The number of firmly adhering leukocytes in retinal veins (152.1± 23.3, n=6) was reduced by 74.3 % over controls (592.1± 95.5, n=6, p<0.001) in GB-treated animals. The number in retinal arteries was lower by 30.5 % in GB-treated animals (16.6 ± 3.0, n=6) than in controls (23.9 ± 4.5, n=6); however, the difference did not reach statistical significance (p<0.2). The number of PSGL-1 conjugated microspheres in the retinal vasculature (148.0 ± 16.6, n=6) was 48 % less in GB-treated animals than in vehicle-treated controls (286.5 ± 25.4, n=4, p<0.001).

Conclusions: : Platelet Activating Factor is critical to the inflammatory leukocyte recruitment in EIU. Our in vivo molecular imaging suggests that P-selectin translocation to the retinal endothelial surface contributes to the effect of PAF. Targeting PAF with GB might become an attractive strategy in treatment and prevention of acute ocular inflammation.

Keywords: inflammation • retina • uveitis-clinical/animal model