Cryogenic lesion alters the metabolism of arachidonic acid in rabbit cornea layers.
The metabolism of radiolabeled arachidonic acid in epithelium, stroma, and endothelium was studied in normal and cryogenically lesioned rabbit corneas. The synthesis of cyclooxygenase- and lipoxygenase-reaction products, as well as the incorporation of arachidonic acid in phospholipids and neutral lipids, was followed by in vitro incubation (60 min) of corneas obtained 2 hr, 5 days, and 15 days after injury. In unwounded controls, prostaglandin E2 (PGE2) was the major cyclooxygenase product formed in the stroma, whereas thromboxane B2 predominated in the endothelium and epithelium. The major lipoxygenase product detected under these conditions in the epithelium was mono-hydroxyeicosatetraenoic acid (mono-HETE) and in the stroma, 12-HETE. In contrast, lipoxygenase products could not be detected in control endothelium. Two hours after injury, the labeling of lipids in epithelium and endothelium decreased; the largest decrease was in phosphatidylinositol, followed by phosphatidylcholine and phosphatidylethanolamine. At the same time, cyclooxygenase-reaction products in the epithelium increased, particularly PGF2 alpha. Prostaglandin levels in the stroma rose rapidly after injury and remained elevated for 15 days. In the endothelium, increases in PGF2 alpha and PGE2 were the most prominent effects of injury. After wounding, lipoxygenase products appeared for the first time in the endothelium and increased in the stroma and epithelium. Within 2 hr after lesioning, 12-HETE and 5-HETE increased in stroma. These studies show that the metabolism of arachidonic acid is altered by cryogenic injury and that the resulting changes differ in the three layers of the cornea. These changes involve arachidonoyl groups of phospholipids and cyclooxygenase and lipoxygenase products, and it is suggested that they are at least partly due to the migration of inflammatory cells to the wound site.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002465:Cell Movement; D003315:Cornea / Q000166:cytology / Q000378:metabolism*; D003319:Corneal Stroma / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D050356:Lipid Metabolism; D008084:Lipoxygenase / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011453:Prostaglandins / Q000096:biosynthesis; D011817:Rabbits; D013997:Time Factors
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases