title: Prevention of experimental diffuse lamellar keratitis using a novel platelet-activating factor receptor antagonist.
abstract: OBJECTIVE
  To determine whether a novel platelet-activating factor (PAF) antagonist prevents experimentally induced diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK).
  
  
  METHODS
  Department of Ophthalmology and Neuroscience Center of Excellence, Louisiana State University Health Science Center, New Orleans, Louisiana, USA.
  
  
  METHODS
  Twenty eyes of 10 New Zealand albino rabbits were used. The left eyes were treated with a peribulbar injection of 0.5 mL of PAF receptor antagonist LAU 0901 (2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid ester) dissolved in 20 hydroxypropyl B cyclodextrin (30 microg /mL). Two rabbits were treated with a peribulbar injection of 0.5 mL of vehicle (cyclodextrin) alone and served as controls. A corneal flap was cut in all eyes, and the interface was exposed to Pseudomonas aeruginosa endotoxin. The left eyes were additionally treated with 1 drop of LAU 0901 4 times a day. Rabbits were killed on postoperative days 1, 2, 3, 5, and 8. The eyes were enucleated and processed for histopathology and immunohistochemical examination.
  
  
  RESULTS
  Corneas not treated with LAU 0901 and controls showed a severe inflammatory response in the flap margin and stromal interface, characterized by loss of keratocytes, activation of adjacent keratocytes and transformation to myofibroblasts, infiltration of polymorphonuclear leukocytes and monocytes, and presence of epithelial cells with necrosis and melting of adjacent stroma. Corneas of rabbits treated with LAU 0901 showed minimal loss of keratocytes and myofibroblast transformation, minimal inflammatory cell infiltration, and minimal presence of epithelial cells in the interface.
  
  
  CONCLUSIONS
  Induction of DLK was blocked by a PAF receptor antagonist in rabbit eyes. The histopathological evaluation and immunohistochemical studies showed that treatment with LAU 0901 blocked keratocyte apoptosis, transformation of fibroblasts to myofibroblasts and migration to the wound site, and chemotaxis of inflammatory cells, inhibiting the inflammatory response and promoting adequate healing of the flap interface and adjacent stroma.
authors.affiliation: Department of Ophthalmology and Neuroscience Center of Excellence, LSU Health Science Center, Louisiana State University School of Medicine, 2020 Gravier Street 3rd Floor, Suite B, New Orleans, LA 70112, USA.
authors.forename: Salomon
authors.initials: S
authors.lastname: Esquenazi
authors.forename: Jiucheng
authors.initials: J
authors.lastname: He
authors.forename: Haydee E P
authors.initials: HE
authors.lastname: Bazan
authors.forename: Nicolas G
authors.initials: NG
authors.lastname: Bazan
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D004095:Dihydropyridines / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004731:Endotoxins; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D007634:Keratitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009883:Ophthalmic Solutions; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011549:Pseudomonas; D011817:Rabbits; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000199:Actins; D004095:Dihydropyridines; D004731:Endotoxins; C487837:LAU 0901; D009883:Ophthalmic Solutions; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D002809:Chondroitin Sulfates