Prevention of lens protein-induced ocular inflammation with cyclooxygenase and lipoxygenase inhibitors.
By the use of fluorophotometry, ocular inflammation induced by lens proteins can be objectively quantified. This method of measuring inflammation was applied to studying the effectiveness of a cyclooxygenase inhibitor, indomethacin, and a lipoxygenase inhibitor, REV 5901, in reducing ocular inflammation induced by lens proteins. Pretreatment with indomethacin prevented the leakage of fluorescein into the anterior chamber up to 2 hrs after intracameral injection of lens proteins. After the first 2 hrs, fluorescein concentration in the pretreated eye rapidly increased to equal the control eye by 4 hrs. When REV 5901 was used to pretreat the eye, there was an increase in fluorescein leakage up to 3 hrs after lens protein injection. However, when a combination of indomethacin and REV 5901 was used to pretreat the eye, there was a significant reduction in fluorescein leakage up to 5 hrs after the injection of lens proteins. The reduction of fluorescein leakage with a combination of indomethacin and REV 5901 was greater than that obtained with prednisolone alone. These results indicate that prostaglandins are the primary mediators of inflammation in the early phase (less than 3 hr) of lens protein induced ocular inflammation and leukotrienes are the primary mediators in the late phase (greater than 3 hr) of lens protein induced ocular inflammation. Also the use of a nonsteroidal antiinflammatory drug which blocks only one arm of the arachidonic acid cascade may potentiate the production of metabolites in the other arm of the cascade. By using a combination of a cyclooxygenase inhibitor and a lipoxygenase inhibitor, metabolites from both arms of arachidonic acid cascade are reduced, hence reducing inflammation in both the early phase and late phase of lens protein induced ocular inflammation.
Chang
M S
MS
Department of Medical Pharmacology and Toxicology, Texas A&M University College of Medicine, College Station.
Chiou
G C
GC
D000818:Animals; D003459:Crystallins; D016861:Cyclooxygenase Inhibitors; D004359:Drug Therapy, Combination; D005128:Eye Diseases / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D005452:Fluoresceins; D015590:Fluorophotometry; D006912:Hydroxyquinolines / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D016859:Lipoxygenase Inhibitors; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use; D011804:Quinolines; D011817:Rabbits
D003459:Crystallins; D016861:Cyclooxygenase Inhibitors; D005452:Fluoresceins; D006912:Hydroxyquinolines; D016859:Lipoxygenase Inhibitors; D011804:Quinolines; C049740:alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol; D011239:Prednisolone; D007213:Indomethacin