Platelet Activating Factor (PAF) Receptor Antagonism Modulates Inflammatory Signaling in Experimental Uveitis
| Autor: | Maria Reinoso, Jennifer J Lentz, Kristopher G. Sheets, Nicolas G. Bazan, J. Elison, Cornelius E. Regan, William C. Gordon, Jessica E. Weinstein |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Dihydropyridines genetic structures medicine.drug_class Vascular permeability Inflammation Platelet Membrane Glycoproteins Pharmacology Hypopyon Article Receptors G-Protein-Coupled Aqueous Humor Uveitis 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine medicine Animals Platelet-activating factor business.industry Tumor Necrosis Factor-alpha Receptor antagonist medicine.disease Sensory Systems eye diseases Neuroprotection Rats Ophthalmology Disease Models Animal 030104 developmental biology chemistry Rats Inbred Lew Adjunctive treatment 030221 ophthalmology & optometry Tumor necrosis factor alpha sense organs medicine.symptom business Signal Transduction |
| Popis: | BACKGROUND: The phospholipid mediator platelet activating factor (PAF) activates an inflammatory response that includes arachidonic acid release and prostaglandin production in the eye, increasing vascular permeability and inflammation. The purpose of this study is to investigate the action of LAU-0901, a novel PAF receptor antagonist, on experimental uveitis. METHODS: Uveitis was induced in Lewis rats by lipopolysaccharide (LPS) treatment. LAU-0901 was then delivered systemically in different concentrations at plus 4 and 16 hours, or vehicle injected as controls. Additional animals were used for histological analyses of untreated, uveitis, and uveitis-plus-LAU-0901 retinas. Conventional histological and immunohistochemical methods were employed. A slit lamp and Spectral Domain-Ocular Coherence Tomography (SD-OCT) retinal imager was used for anterior segment photography and posterior pole OCT. Rats were euthanized 4 hours after the second LAU-0901 injection in this 24-hour model. Aqueous humor was collected and quantified, and also analyzed for tumor necrosis factor alpha (TNF-α). RESULTS: Uveitic eyes demonstrated hypopyon formation, leukocyte infiltration, and an increase in aqueous protein and TNF-α levels. LAU-0901 treatment resulted in a dose-dependent reduction in inflammation, reflected by reduced total protein levels (up to a 64% reduction). Moreover, hypopyon was prevented, leukocytes were absent in vitreous and aqueous humor, and TNF-α levels were reduced by 91%. CONCLUSIONS: The PAF receptor antagonist LAU-0901 decreases ocular inflammation in a rat model of anterior uveitis in a dose-dependent manner, suggesting that use of this molecule may provide a means to attenuate inflammation onset and offer a future alternative or adjunctive treatment for ocular inflammation. |
| Databáze: | OpenAIRE |
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