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S. Esquenazi, J. He, N. Li, W. Rand, N. Bazan, I. Esquenazi, H. Bazan; A Novel Platelet- Activating Factor (PAF) Receptor Antagonist Reduces Cell Infiltration and Expression of Inflammatory Mediators in Mice Exposed to Desiccating Condition After Prk. Invest. Ophthalmol. Vis. Sci. 2008;49(13):438.
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Previous studies have shown that PAF is a potent inflammatory mediator in the cornea that acts through specific receptors and stimulates cell infiltration and expression of cyclooxygenease-2 (COX-2). We had demonstrated that there is an increase in cell infiltration and COX-2 expression in mice corneas exposed to desiccating conditions (DE) following photorefractive keratectomy (PRK). Therefore, we examined if a novel PAF receptor antagonist, LAU-0901, could modulate the inflammatory response in these conditions.
Eighty 13-14 week old female Balb/C mice were used in this study. They were divided into two groups: One group was treated with LAU-0901 topical drops 4 times a day for 1 week. The other group was treated with vehicle. From each group, ten served as controls and ten were placed in DE. The other twenty mice underwent bilateral PRK and were divided into two additional sub-groups: ten mice were placed in normal conditions (NC) and the other ten mice were exposed to DE. Western blotting and immunohistochemistry studies were performed using CD45, GR-1, CD 11b CD 11c, COX-2 and α-SMA antibodies.
Reduced numbers of leukocytes (CD 45+) , CD 11b+(macrophages and dendritic cells) and GR-1+ cells (neutrophils) were found in the stroma of eyes with epithelial injury and exposed to DE that were treated with LAU-0901 in comparison with the non-treatment group. There was also a decrease in the expression of COX-2 in the epithelium and α-SMA positive cells (myofibroblasts) in stroma.
Our results suggest that PAF is involved in the inflammatory cell infiltration and expression of inflammatory cytokines that follow PRK under DE, and that in blocking the inflammatory cascade with LAU-0901, there is also reduced generation of myofibroblasts in the corneal stroma. This event may have implications in the predictability and stability of the refractive results.
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