CORNEAL ARACHIDONIC ACID METABOLISM

这项拨款的目的是确定：(1)花生四烯酸如何

The objectives of this grant are to determine: (1) how arachidonic acid (AA) metabolism is regulated in normal rat corneal epithelium; (2) what changes occur in arachidonate metabolism following corneal cauterization; and (3) whether nonsteroidal anti-inflammatory drugs can prevent corneal inflammation and vascularization by inhibiting AA metabolism. Regulation of AA metabolism will be studied in intact epithelium isolated by neutral-protease treatment of corneas. Cellular phospholipids will be labeled with [3H]AA and a variety of substances will be tested to determine if they activate phospholipase A2 with resultant release of free AA. Phospholipase A2 activation is a key step in regulation of AA metabolism and is potentially amenable to pharmacological inhibition. Another project will use potassium/silver nitrate cauterization of rat corneas to investigate changes in AA metabolism occurring prior to the influx of inflammatory cells. Metabolism of exogenous [3H]AA will be quantitated and, in addition, we will develop an assay for measuring L-3-phosphatidylcholine, 1-stearoyl-2-[3H]arachidonyl metabolism. These two complimentary approaches will allow us to detect injury-induced changes in phospholipase A2 activation and lipoxygenase/cyclooxygenase pathway activity. A final study will examine the influence of lipoxygenase inhibitors, cyclooxygenase inhibitors, and a dual cyclooxygenase-lipoxygenase inhibitor on corneal inflammation and vascularization following cauterization of rat corneas. Changes in AA metabolism during the inflammatory and vascularization responses will also be studied using animals treated with normal saline (drug vehicle) only. These studies will determine whether AA metabolites are important mediators of corneal inflammation and vascularization and will clarify the potential usefulness of nonsteroidal antiinflammatory drugs for treating corneal injuries.