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L.M. Velasquez, S.D. Klyce, M.D. Karon, C.B. Courville; Mediation of Stromal Swelling Following Corneal Epithelial Trauma. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):127.
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Purpose: Corneal epithelial trauma leads to a variety of inflammatory responses including an acute, localized stromal edema, which previous studies have shown can be blocked with certain inhibitors of several pathways. In this study inhibition of inducible Nitric Oxide Synthetase (iNOS) , as well as dual inhibitors, are examined to determine the possible potentiation of anti–inflammatory effects. Methods: The eyelids of anesthetized adult New Zealand White rabbits were briefly opened to apply a drop (50µl) of control or experimental solution in each cul de sac every 45 minutes for a 3 hr period. Ringer’s solution was used as perfusate and drug vehicle. In one series the iNOS inhibitor, aminoguanidine hemisulfate (1 mM, Sigma) was administered to one eye, while Ringer’s solution by itself was applied to the other eye as a control. In the second series, 2 mM of the synthetic inhibitor of metalloproteinase, SIMP–1 (Peptides international) was used as a control and the combination of SIMP–1 and Diclofenac Sodium 0.1% (Ciba Vision) was used in the test eye. After the rabbits were euthanized, their corneas were mounted in perfusion chambers with the endothelium bathed in Ringer’s solution and the epithelium covered with silicone oil. Corneal thickness was measured with an automatic specular microscope. After 1 hr for stabilization, the corneal epithelia were debrided with a rotating bristle brush to produce the injury response and stromal thickness was measured for an additional 1 hr period. Paired controls were treated similarly and the paired t–test was used. Results: Treatment with iNOS reduced the swelling response to 23.7±4.3 µm compared to the Ringer’s control of 32.4 ± 8.6 µm (n=9; p=0.019). The combination of SIMP–1 with Diclofenac sodium also protected against some of the stromal edema (21.1 ± 9.1µm) compared to the use of SIMP–1 alone (30.5 ± 8.3 µm; n=7; p=0.016). Conclusions: Aminoguanidine, which blocks the expression of iNOS, is able to block the proinflammatory effect of epithelial injury when used topically. In addition, the potentiation of the anti–inflammatory effect of metalloproteinase inhibition by a non–selective cylcooxygenase inhibitor underscores the plurality of active inflammatory pathways in the cornea.
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