Abstract
Purpose: :
To evaluate the effect of a selective PAF receptor antagonist LAU-0901 (SCP-09001) on an in vivo mouse model of corneal epithelial and stroma injury.
Methods: :
C57BL/6 mice were injured by scraping the corneal epithelium and anterior stroma (about 25 %) using an Algerbrush II under a surgical microscope. Mice were divided into three groups: to the first group, PAF (10 µg/ml, 2x 5 µl) was applied topically; to the second group, LAU-0901 (30 mg/Kg) was injected i.p. after PAF application; the third group received only vehicle as control. This treatment took place once a day. Additional mice received no injury or treatment. Mice were sacrificed at 1, 2, and 7 days after injury. The corneas were processed for histopathology and immunofluorescence with antibodies for metalloproteinase-9 (MMP-9), fibronectin (FN) and α-smooth muscle actin (α-SMA).
Results: :
One day after injury there was a 50 % delay in epithelial wound closure in presence of PAF compared to vehicle treated animals. The delay was also significant 2 days after the injury. LAU-0901 completely blocked the PAF effect. Treatment with PAF for 2 days increased MMP-9 and decreased FN expression in the epithelium and stroma; consequently, fewer myofibroblasts migrated to the wounded area. By 7 days, MMP-9 was still upregulated and FN was downregulated. All these changes were inhibited when the animals were treated with LAU-0901.
Conclusions: :
PAF is a strong inflammatory mediator and a potent activator of MMP-9 that promotes FN degradation, thereby delaying epithelial wound healing and migration of myofibroblasts from the limbal area. The inhibition of PAF action by LAU-0901 could be important in the treatment of corneal injuries that compromise the stroma.
Keywords: inflammation • extracellular matrix • lipids