HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Karon, M. D. Articles by Klyce, S. D. Search for Related Content PubMed PubMed Citation Articles by Karon, M. D. Articles by Klyce, S. D.

Effect of Inhibition of Inflammatory Mediators on Trauma-Induced Stromal Edema

¹From the Department of Ophthalmology, LSU Health Sciences Center, New Orleans, Louisiana; and the ²Department of Biomedical Engineering, Tulane University, New Orleans, Louisiana.

PURPOSE. To determine the specific biochemical pathways involved in the initial-phase inflammatory response that causes stromal edema after epithelial debridement of the rabbit cornea.

METHODS. Adult New Zealand White rabbit corneas were treated with 2 mM synthetic inhibitor of metalloproteinase (SIMP)-1, 1 mM DFU (a specific cyclooxygenase [COX]-2 inhibitor) in 50/50 dimethyl sulfoxide (DMSO)/Ringer’s solution, 300 KIU aprotinin (a serine protease inhibitor), 0.05% or 0.10% IL-1 receptor type II solution, 1 mM gliotoxin (a Ras farnesyltransferase inhibitor), or vehicle alone (the control). These were applied topically in vivo in five doses over a 3-hour period except IL-1 receptor type II, which was applied in vitro. After rabbits were killed, the corneas were mounted in perfusion chambers with the endothelium bathed in a modified Ringer’s solution and the epithelium bathed with silicone oil. Corneal thickness was measured with an automatic specular microscope. The corneal thickness typically stabilized 1 hour after mounting. After stabilization, the corneal epithelium was removed with a rotating bristle brush and stromal thickness monitored for 1 hour. Paired control corneas were treated similarly.

RESULTS. Stromal swelling after epithelial debridement was significantly less in most treated corneas, compared with untreated controls: 18.4 ± 5.3 µm vs. 28.6 ± 7.7 µm (n = 6, P = 0.004); SIMP-1, 18.7 ± 10.2 µm vs. 34.3 ± 10.2 µm (n = 7, P = 0.02); DFU, 19.3 ± 10.2 µm vs. 23.5 ± 8.4 µm (n = 6, P = 0.01); and IL-1 receptor type II (0.05%), 26.2 ± 5.6 µm vs. 30.4 ± 5.6 µm (n = 5, P = 0.03) and (0.10%), 26.6 ± 5.6 µm vs. 32.1 ± 7.4 µm (n = 8, P = 0.03). Gliotoxin was not effective (21.5 ± 8.0 µm vs. 21.9 ± 6.2 µm; n = 5, P = 0.94).

CONCLUSIONS. The reduction of stromal edema after topical administration of the inhibitors demonstrates the involvement of the COX-2 enzyme, the matrix metalloproteinase family, plasminogens, and the IL-1 system in the trauma-induced inflammatory response of the rabbit cornea. The inflammatory process in the cornea associated with trauma can proceed along multiple redundant parallel pathways.