The research described in this thesis studies the corneal swelling dynamics that arise from the initial-phase inflammatory response following epithelial debridement of the rabbit cornea. Previous work has demonstrated that there is apoptosis of stromal keratocytes as well as stromal swelling following epithelial debridement. For this study's experimental series, adult New Zealand White rabbit corneas were topically treated in-vivo with inflammatory pathway inhibitors---a synthetic inhibitor of metalloproteinases (SIMP-1), a specific COX-2 inhibitor (DFU), a serine protease inhibitor (aprotinin), IL-1 Receptor Type II, a Ras farnesyltransferase inhibitor (gliotoxin), or as a control the specific vehicle used for each of these inhibitors alone. The corneas were mounted in endothelium-perfused chambers; the corneal epithelium was removed using a rotating bristle brush and the bare stromal surface covered with silicone oil to block fluid movement. Subsequently, corneal thickness was monitored over a period of 1 hour. The swelling responses were analyzed using a trend analysis technique as well as a computational model designed to simulate corneal hydration dynamics. The stromal swelling following epithelial debridement was significantly reduced by pre-treatment with aprotinin, SIMP-1, DFU, or IL-1 receptor type II. Gliotoxin was not effective in reducing the stromal edema. The trend analysis concluded that the swelling curves were representative of a biphasic response. The computational model produced a good fit of both the internal and total swelling dynamics by simulating proteolysis and fluid redistribution due to tissue compression. Our results are consistent with involvement of the COX-2 enzyme, the matrix metalloproteinase family, plasminogens, and interleukin-1 in the trauma-induced inflammatory response of the rabbit cornea. (Abstract shortened by UMI.)
