title: Topical amiloride accelerates healing and delays neovascularization in mechanically produced corneal ulcers in rabbits.
abstract: The present investigation was undertaken to explore the ulcer healing and antiangiogenic efficacy of two dosage schedules of topically administered amiloride in mechanically produced corneal ulcers in rabbits and to compare its effect with the conventional topical antiinflammatory angiostatic agent flurbiprofen. The epithelium and superficial lamellae of the stroma of both eyes of each rabbit were cut through by a corneal trephine (8 mm diameter) up to a depth of 0.3 mm and removed after local anesthesia. The animals were randomly divided in groups of 4 rabbits each. In the eyes of 2 groups of animals, amiloride (4%) was instilled either q.i.d. or b.i.d.; in another, flurbiprofen (0.03%) was instilled twice daily whereas the saline-treated group served as control. The healing of ulcer was followed on a slit lamp regarding its size, depth, slough formation, infiltration and neovascularization on alternate days up to the 10th day with and without fluorescein staining. Healing of corneal ulcers was significantly accelerated by both dosage schedules of topical amiloride (4%) but more so following q.i.d. instillation. Topical flurbiprofen, on the other hand, delayed the healing process. Instillation of amiloride four times daily or flurbiprofen twice daily inhibited angiogenesis significantly. However, appearance of new vessels was completely prevented when amiloride (4%) was instilled twice daily. Thus topical amiloride (4%) may prove to be a cheap and better antineovascularization as well as ulcer healing agent with no apparent side effects. Inhibition of uPA by amiloride appears to be responsible for these effects.
authors.affiliation: Department of Ophthalmology, LLRM Medical College, Meerut, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Sood
authors.forename: B
authors.initials: B
authors.lastname: Gupta
authors.forename: P
authors.initials: P
authors.lastname: Chugh
mesh_terms: D000584:Amiloride / Q000493:pharmacokinetics / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D003315:Cornea / Q000098:blood supply / Q000378:metabolism; D003320:Corneal Ulcer / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005480:Flurbiprofen / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011817:Rabbits; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology
chemical_list: D020533:Angiogenesis Inhibitors; D005480:Flurbiprofen; D000584:Amiloride; D014568:Urokinase-Type Plasminogen Activator