title: Platelet recruitment promotes keratocyte repopulation following corneal epithelial abrasion in the mouse.
abstract: Corneal abrasion not only damages the epithelium but also induces stromal keratocyte death at the site of injury. While a coordinated cascade of inflammatory cell recruitment facilitates epithelial restoration, it is unclear if this cascade is necessary for keratocyte recovery. Since platelet and neutrophil (PMN) recruitment after corneal abrasion is beneficial to epithelial wound healing, we wanted to determine if these cells play a role in regulating keratocyte repopulation after epithelial abrasion. A 2 mm diameter central epithelial region was removed from the corneas of C57BL/6 wildtype (WT), P-selectin deficient (P-sel-/-), and CD18 hypomorphic (CD18hypo) mice using the Algerbrush II. Corneas were studied at 6h intervals out to 48h post-injury to evaluate platelet and PMN cell numbers; additional corneas were studied at 1, 4, 14, and 28 days post injury to evaluate keratocyte numbers. In WT mice, epithelial abrasion induced a loss of anterior central keratocytes and keratocyte recovery was rapid and incomplete, reaching ~70% of uninjured baseline values by 4 days post-injury but no further improvement at 28 days post-injury. Consistent with a beneficial role for platelets and PMNs in wound healing, keratocyte recovery was significantly depressed at 4 days post-injury (~30% of uninjured baseline) in P-sel-/- mice, which are known to have impaired platelet and PMN recruitment after corneal abrasion. Passive transfer of platelets from WT, but not P-sel-/-, into P-sel-/- mice prior to injury restored anterior central keratocyte numbers at 4 days post-injury to P-sel-/- uninjured baseline levels. While PMN infiltration in injured CD18hypo mice was similar to injured WT mice, platelet recruitment was markedly decreased and anterior central keratocyte recovery was significantly reduced (~50% of baseline) at 4-28 days post-injury. Collectively, the data suggest platelets and platelet P-selectin are critical for efficient keratocyte recovery after corneal epithelial abrasion.
authors.affiliation: Baylor College of Medicine Department of Pediatrics, Section of Leukocyte Biology, 1100 Bates, CNRC 6058, Houston, Texas, 77030, United States of America; Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey VA Medical Center, 2002 Holcombe Blvd., MS 151, Houston, Texas, 77030, United States of America.
authors.forename: Fong W
authors.initials: FW
authors.lastname: Lam
authors.affiliation: University of Houston College of Optometry, 505 J Davis Armistead Bldg, Houston, Texas, 77204, United States of America; University of Wisconsin, Department of Pathology, 1300 University Ave., Room 6550, Madison, Wisconsin, 53706-1532, United States of America.
authors.forename: Jenny
authors.initials: J
authors.lastname: Phillips
authors.affiliation: University of Houston College of Optometry, 505 J Davis Armistead Bldg, Houston, Texas, 77204, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Landry
authors.affiliation: University of Houston College of Optometry, 505 J Davis Armistead Bldg, Houston, Texas, 77204, United States of America.
authors.forename: Sri
authors.initials: S
authors.lastname: Magadi
authors.affiliation: Baylor College of Medicine Department of Pediatrics, Section of Leukocyte Biology, 1100 Bates, CNRC 6058, Houston, Texas, 77030, United States of America.
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Smith
authors.affiliation: Baylor College of Medicine Department of Pediatrics, Section of Leukocyte Biology, 1100 Bates, CNRC 6058, Houston, Texas, 77030, United States of America; Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey VA Medical Center, 2002 Holcombe Blvd., MS 151, Houston, Texas, 77030, United States of America.
authors.forename: Rolando E
authors.initials: RE
authors.lastname: Rumbaut
authors.affiliation: Baylor College of Medicine Department of Pediatrics, Section of Leukocyte Biology, 1100 Bates, CNRC 6058, Houston, Texas, 77030, United States of America; University of Houston College of Optometry, 505 J Davis Armistead Bldg, Houston, Texas, 77204, United States of America.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Burns
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D065306:Corneal Injuries / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D060527:Corneal Keratocytes / Q000166:cytology / Q000473:pathology*; D019573:Epithelium, Corneal / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D017353:Gene Deletion; D008297:Male; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000235:genetics / Q000276:immunology; D014945:Wound Healing
chemical_list: D019007:P-Selectin