Effect of inhibitors of arachidonic acid metabolism on corneal neovascularization in the rat.
We used computerized image analysis to evaluate quantitatively the ability of topically applied corticosteroids (dexamethasone sodium phosphate, prednisolone acetate), cyclooxygenase inhibitors (flurbiprofen, indomethacin, ketorolac), lipoxygenase inhibitors (REV 5901, esculetin, quercetin), and dual cyclooxygenase/lipoxygenase inhibitors (BW 755C, BW A540C) to reduce corneal neovascularization in the rat induced by silver/potassium nitrate cauterization. Significant decreases in the neovascular response were found with corticosteroids and cyclooxygenase inhibitors. A complete dose-response curve was performed for a representative compound from each class. Dexamethasone was found to be superior to flurbiprofen in its ability to reduce neovascularization in this model, while no significant inhibition was noted with either REV 5901 or BW 755C, even at high doses. We conclude that the corneal angiogenic response in this model can be reduced by inhibition of cyclooxygenase as well as by other mechanisms that are steroid-dependent but are, as yet, poorly defined.
Haynes
W L
WL
Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina.
Proia
A D
AD
Klintworth
G K
GK
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003315:Cornea / Q000098:blood supply* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007091:Image Processing, Computer-Assisted; D008084:Lipoxygenase / Q000494:pharmacology; D008297:Male; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D009566:Nitrates / Q000009:adverse effects; D017680:Potassium Compounds; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology; D051381:Rats; D012835:Silver Nitrate / Q000009:adverse effects
D000305:Adrenal Cortex Hormones; D001095:Arachidonic Acids; D009566:Nitrates; D017680:Potassium Compounds; D012835:Silver Nitrate; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; C023844:potassium nitrate