An ex-vivo, whole-globe porcine model of corneoepithelial wound healing tested using immunomodulatory drugs

• Published in: Journal of ocular pharmacology and therapeutics Vol. 21; no. 5; p. 367
• Main Authors: Flueckiger, Franziska, Kodjikian, Laurent, Halberstadt, Markus, Boehnke, Matthias, Garweg, Justus G
• Format: Journal Article
• Language: English
• Published: United States 01.10.2005
• Subjects: Animals; Cyclosporine - pharmacology; Dexamethasone - pharmacology; Dose-Response Relationship, Drug; Epithelium, Corneal - drug effects; Epithelium, Corneal - injuries; Mitomycin - pharmacology; Models, Animal; Swine; Wound Healing - drug effects
• ISSN: 1080-7683; 1557-7732
• DOI: 10.1089/jop.2005.21.367

An efficient epithelial wound healing is essential for the preservation of vision. Hence, the effects of novel topical drugs on the ocular surface must be ascertained before clinical use. We have tested the utility of an ex vivo, whole-globe porcine screening model to serve as a partial substitute for resource- and time-consuming animal experiments. Standardized corneoepithelial lesions, 5.0 mm in diameter and 40 microm in depth, were created with an Excimer laser in freshly enucleated porcine eyes. These were then exposed to control solutions (physiological saline (baseline), tissue-culture medium (positive control) and NH4 + (toxicity control)) and to three test agents (cyclosporin A, dexamethasone, and mitomycin C). The wound-healing response and toxic effects were monitored after 20-26 h by comparing lesion sizes. According to baseline data obtained using physiological saline, tissue-culture medium improved wound healing. The highest doses of NH4 + (1 M) and mitomycin C (1.0 mg/mL) elicited toxic effects (confidence interval according to Scheffé's post hoc test: -0.65 to -0.07 and -0.99 to -0.60, respectively). Under the same test conditions, cyclosporin A (0.1 to 10 mg/mL) and dexamethasone (0.1 to 10 mg/mL) had no influence on corneoepithelial wound healing. Drug screening with this ex vivo porcine model permits a reproducibly quantitative and time- and dose-dependent assessment of corneoepithelial wound healing. This model corresponds more closely to the clinical situation than cell culturing and may, therefore, be useful in evaluating novel pharmaceutical agents, thereby helping to cut down on the number of animal experiments performed prior to the instigation of clinical trials.