Abstract
Purpose: :
Lipid mediators such as platelet activating factor (PAF) are components of the inflammatory response. PAF activates the release of arachidonic acid and the production of prostaglandins in the eye, increasing vascular permeability and inflammation. The purpose of this study is to investigate the action of LAU0901 (a novel small molecule PAF receptor antagonist) in the treatment of uveitis.
Methods: :
Uveitis was induced in Lewis rats by injecting 100µl (200µg) of lipopolysaccharide (LPS) into their right hind paw. 1µl/g of LAU0901 was injected intraperitoneally at different concentrations 4 hours after LPS injection and was repeated 16 hours after the first injection. Groups of 5 animals were injected with 15µg/µl, 30µg/µl, 45µg/µl, and 60µg/µl. Five rats were also used as non-uveitis controls, and 5 were injected intraperitoneally with vehicle (45% cyclodextran). This same experiment was repeated with the same number of animals (total n = 10 animals, 20 eyes). Spectral Domain Ocular Coherence Tomography (SD OCT) (Heidelberg Engineering) was used for anterior segment photography and posterior pole OCT. Rats were euthanized 4 hours after the second LAU0901 injection in this 24 hour model, and aqueous humor was collected. Aqueous protein was quantified using the BioRad Protein Assay using an Eppendorf Biophotometer. A 1:500 dilution of the aqueous humor was used.
Results: :
Control eyes with uveitis demonstrated hypopyon formation, vitreous cells on OCT imaging, and an increase in total protein levels. LAU0901 treatment resulted in a dose-dependent reduction in inflammation, measured by total protein levels. Animals treated with the 60µg/µl dose had a 64% reduction in total protein levels compared with controls.
Conclusions: :
The PAF antagonist LAU0901 decreases ocular inflammation in a rat model of anterior uveitis in a dose-dependent manner. LAU0901 may be a future alternative or adjunctive treatment for ocular inflammation.
Keywords: uveitis-clinical/animal model • lipids • inflammation