Prevention of experimental diffuse lamellar keratitis using a novel platelet-activating factor receptor antagonist.

摘要

Purpose: To determine whether a novel platelet-activating factor (PAF) antagonist prevents experimentally induced diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK). Settings: 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. Conclusion: 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.