Abstract
Abstract: :
Purpose: Inflammation plays an important role in corneal wound repair. We examined contributions of CD11a/CD18 (LFA–1) and CD11b/CD18 (Mac–1), important leukocyte integrins, in corneal epithelial wound healing in mice. Methods: The central corneal epithelium (2 mm diameter) was demarcated and removed in C57Bl/6 wild type, CD11a –/– and CD11b–/– mice. Epithelial healing was digitally analyzed every 6 hours. The infiltration of neutrophils into wounds was quantified under deconvolution microscopy. Enzyme–linked immunosorbent assay (ELISA) was used to measure IL–1, IL–6, IL–8, MCP–1, MIP–2, and LIX in corneal extracts. Results: In both CD11a–/– and CD11b–/– mice, neutrophil emigration, cytokine levels and chemokine levels were significantly delayed, peaking at 24 hours after wounding (p<0.01) compared to wildtype mice peaking at 12 hours. In wild type, re–epithelialization occurred by 18–24 hours, but was delayed (p<0.01) in both knockout mice by an additional 6–12 hours (CD11a–/–) and 24–48 hours (CD11b–/–). Neutrophil numbers were markedly reduced in CD11a–/– (p<0.01) but markedly elevated in CD11b–/– mice (p<0.01) compared to wild type. Conclusions: LFA–1 is required for efficient neutrophil emigration into cornea, but Mac–1 is not. Mac–1 appears to be important in limiting the inflammatory response. Absence of either integrin significantly delays re–epithelization.
Keywords: cornea: epithelium • inflammation • wound healing