Role of platelet-activating factor in cell death signaling in the cornea: A review

Salomon Esquenazi1, Haydee E P Bazan

  • 1Neuroscience Center of Excellence and Department of Ophthalmology, LSU Health Sciences Center, New Orleans, LA, USA.

Insights

Platelet-activating factor (PAF) promotes corneal cell death and delays wound healing. PAF antagonists may protect the cornea by blocking these effects, preserving transparency.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Wound Healing Research

Background:

  • Platelet-activating factor (PAF) is a lipid mediator released in the cornea post-injury.
  • PAF signaling through its receptors triggers transmembrane signals linked to apoptosis.
  • Prolonged PAF exposure during inflammation impairs corneal wound healing.

Purpose of the Study:

  • To investigate the role of PAF in corneal cell apoptosis and wound healing.
  • To determine the mechanisms by which PAF affects corneal epithelial cells and myofibroblasts.
  • To evaluate the therapeutic potential of PAF antagonists in corneal repair.

Main Methods:

  • Analysis of PAF-induced apoptosis in corneal cells (keratocytes, epithelial cells, myofibroblasts).
  • Investigation of PAF's interaction with phospholipase A2, mitochondria, and caspase-3 activation.
  • Assessment of PAF's synergistic effects with TNF-alpha in myofibroblast apoptosis.
  • Evaluation of PAF antagonist efficacy in blocking PAF-mediated effects.

Main Results:

  • Continuous PAF exposure causes keratocyte apoptosis and inhibits epithelial adhesion, delaying wound healing.
  • Corneal epithelial cells and myofibroblasts show differential resistance to PAF-induced apoptosis.
  • PAF accelerates apoptosis in epithelial cells under oxidative stress via phospholipase A2, cytochrome C, and caspase-3.
  • PAF synergizes with TNF-alpha to induce significant apoptosis (85%) in myofibroblasts.

Conclusions:

  • PAF plays a critical role in corneal inflammation-induced apoptosis and delayed wound healing.
  • PAF antagonists offer a potential therapeutic strategy for maintaining corneal transparency and health.
  • Targeting PAF signaling could be beneficial in managing corneal injuries and inflammatory conditions.

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