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H. Bazan, J. He, N.G. Bazan; Prevention of alkali–induced corneal melting by a novel platelet–activating factor (PAF) antagonist. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1421.
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Purpose: Alkali burn of the cornea induces a strong inflammatory reaction. Progression of the injury leads to corneal ulceration and perforation. The lipid mediator PAF accumulates in the cornea after alkali injury and LAU0901, a novel PAF– receptor antagonist, can prevent experimental DLK induced by LASIK ( Esquenazi et al, J Refract Surg, in press). The present study evaluates the effect of LAU0901 on a severe model of corneal alkali injury. Methods: New Zealand albino rabbits (30) were anesthetized and the right eyes were injured with 2N NaOH for 1 minute. After the burn, 10 rabbits were treated topically with LAU0901 (30mg/ml) every 2 hours 4x day plus a subconjunctival injection of 200 µl of LAU0901 once a week; and 10 rabbits treated with vehicle the same way. During 4 weeks rabbits were examined daily using slit–lamp microscopy and corneal ulcers were graded with a clinical score of 0 = no ulcer, 1 = superficial ulceration, 2 = moderate ulceration , 3 = deep ulceration , 4 = descemetocele, 5 = perforation. The rest 10 rabbits used for histopathologic analysis were also assigned to two groups and treated as above, but one rabbit from each groupwas killed at 1, 3, 7, 14 or 21 days after injury. The corneas were processed for histopathologic and immunohistochemical examination. Results: During the course of the experiment, none of the eyes became infected. Persistent epithelial defects were present in both groups from day 5 post–injury, but from day 9 through day 21, the average clinical score in the vehicle–treated eyes were significantly higher than those in the LAU0901–treated eyes. By day 23, 9 of 10 corneas in the vehicle–treated group perforated, but only 2 of 10 corneas in the LAU0901–treated group developed deep ulceration (and none were perforated). Histologic sections of vehicle–treated corneas revealed a dense inflammatory cell infiltration. Numerous PMNs were present throughout the stroma and accumulated at the edge of ulcers. In contrast, there were significantly fewer inflammatory cells present in the LAU0901–treated corneas that were mainly located in the anterior half of the stroma. Conclusions: A new PAF antagonist inhibits corneal ulceration and perforation in an alkali burn model in the rabbit. In the cornea PAF is a strong inflammatory mediator, a chemotactic to PMNs, and an inducer of several proteases that degrade the extracellular matrix. The inhibition of PAF action with LAU0901 could be important in the immediate and intermediate treatment of chemical injuries to preserve the integrity of the cornea.
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