title: Role of platelet-activating factor in cell death signaling in the cornea: A review.
abstract: Platelet-activating factor (PAF) is a potent bioactive lipid generated in the cornea after injury whose actions are mediated through specific receptors. Studies from our laboratory have shown that PAF interactions with its receptors activate several transmembrane signals involved in apoptosis. Continuous exposure to PAF during prolonged inflammation increases keratocyte apoptosis and inhibition of epithelial adhesion to the basement membrane. As a consequence, there is a marked delay in wound healing, which is not countered by the action of growth factors. While apoptosis of stroma cells is rapid and potent, epithelial cells as well as myofibroblasts, which appear in the stroma during the repair phase, are resistant to apoptosis. However, PAF accelerates apoptosis of corneal epithelial cells exposed to oxidative stress by stimulating phospholipase A2, producing an early release of cytochrome C from mitochondria and activating caspase-3. In myofibroblasts, PAF has a synergistic action with tumor necrosis factor-alpha (TNF-alpha), increasing apoptosis of the cells to 85%. PAF antagonists block the effects of PAF and could have a therapeutic role in maintaining a healthy and transparent cornea.
authors.affiliation: Neuroscience Center of Excellence and Department of Ophthalmology, LSU Health Sciences Center, New Orleans, LA, USA.
authors.forename: Salomon
authors.initials: S
authors.lastname: Esquenazi
authors.forename: Haydee E P
authors.initials: HE
authors.lastname: Bazan
mesh_terms: D000818:Animals; D016923:Cell Death; D003315:Cornea / Q000378:metabolism* / Q000473:pathology*; D003319:Corneal Stroma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D054467:Phospholipases A2 / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D010972:Platelet Activating Factor; D054467:Phospholipases A2