|Smith, C wayne|
Submitted to: Investigative Ophthalmology and Visual Science
Publication Type: Peer reviewed journal
Publication Acceptance Date: 7/16/2006
Publication Date: 11/1/2006
Citation: Li, Z., Rumbaut, R.E., Burns, A.R., Smith, C.W. 2006. Platelet response to corneal abrasion is necessary for acute inflammation and efficient re-epithelialization. Investigative Opthalmology and Visual Science. 47:4794-4802. Interpretive Summary: This paper demonstrates for the first time that inflammation and wound healing in the cornea is dependant in part on blood platelets. This inflammation and wound healing is delayed in obese mice, and investigations of the basic mechanisms of the process are necessary, preliminary to an investigation of the mechanisms by which obesity delays healing.
Technical Abstract: Purpose: Adhesion molecules play a critical role in leukocyte emigration to wound sites, but differences are evident in different vascular beds. This study investigates the contributions of P-selectin to neutrophil emigration into the cornea following central epithelial abrasion. Methods: Re-epithelialization, neutrophil influx, and platelet accumulation were assessed in C57Bl/6 mice following removal of a 2 mm diameter area of central corneal epithelium that did not directly injure the limbal vessels or the avascular stroma of the cornea. Comparisons were made between wildtype (WT) mice and mice with targeted deletions of genes for P-selectin, CD18 or CD54, or in mice with antibody-induced neutropenia or thrombocytopenia. Results: Following central corneal epithelial abrasion platelets localized in the limbal vessels and neutrophils emigrated from the limbal vessels to the region of the epithelial wound. There was temporal correspondence of platelet and neutrophil localization, peaking within 12 hours of wounding. Platelet accumulation, neutrophil emigration and corneal epithelial healing as measured by wound closure, basal epithelial cell density and epithelial cell division were significantly reduced in P-selectin-deficient mice (P-sel-/-). Anti-GP1b(alpha) antibody-induced thrombocytopenia in WT mice significantly reduced platelet and neutrophil accumulation and wound healing. Passive transfer of wild type platelets into P-sel-/- mice significantly restored platelet localization in limbal vessels, neutrophil emigration, epithelial cell division, and epithelial cell migration into the abraded region of the cornea. Conclusion: Platelet localization in the limbus of abraded corneas contributes to re-epithelialization, and P-selectin provides a necessary step in this process.