The role of platelet-activating factor in the corneal response to injury.
Platelet-activating factor (PAF) is a potent bioactive lipid that is generated in the cornea after injury and whose actions are mediated through specific receptors. Studies from our laboratory have shown that PAF interactions with its receptor activate several transmembrane signals involved in inflammation, wound healing, and apoptosis. The wide variety of responses to PAF implicate this lipid as a central player in many responses of the cornea after a pathologic stimulus. An exciting facet of PAF is that it induces the expression of specific genes involved in the remodeling of components of the extracellular matrix, such as some metalloproteinases, urokinase plasminogen activator, and selective inhibitors of metalloproteinases. These enzymes, when overexpressed, could lead to corneal ulceration. Continuous exposure to PAF during prolonged inflammation produces increase 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 actions of growth factors. In this review, we present data mainly from our laboratory showing actions of PAF in corneal epithelium in vivo and in vitro in corneal models of injury as well as in cells in culture. We also discuss the signal-transduction mechanisms involved in the different actions of PAF. A therapeutic role for PAF antagonists in blocking the effects of PAF is guaranteed in the future.
Department of Ophthalmology and Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
Haydee
H
Bazan
Paulo
P
Ottino
D000818:Animals; D003315:Cornea / Q000503:physiopathology*; D065306:Corneal Injuries; D005131:Eye Injuries / Q000503:physiopathology*; D010972:Platelet Activating Factor / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics
D010972:Platelet Activating Factor