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S. Chakravarti, N. Vij, L. Roberts, F. Wu, L. Savino; Lumican Regulates Wound Healing and Innate Immune Responses in the Cornea . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2129.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Lumican is a keratan sulfate proteoglycan found in barrier tissues such as the cornea. Its biologically active leucine–repeat rich (LRR) domain binds collagen, and possibly other proteins, with as yet unknown biological implications. We hypothesize that lumican through interactions of the core protein with other cell surface receptors and microbes, play a critical role in the host’s first line of defense. To test this hypothesis we examined corneal healing of wounds exposed to bacterial lipopolysacharides (LPS) in lumican–null (Lum–/–) and wild type (WT) mice. Methods: Circular and incision type stromal wounds, were exposed to P. aeruginosa lipopolysaccharide (LPS) and healing was assessed by (1) following wound closure by fluorescent and bright field microscopy, (2) histology to quantify inflammatory infiltrates by immunostaining for macrophages (F4/80) and neutrophils (NIMP–R14) and Myeloperoxidase (MPO) levels by ELISA to further quantify neutrophils, (3) measuring pro–inflammatory cytokines by ELISA. Results: Circular Stromal wounds showed little change in diameter 72 hours after injury in Lum–/– mice, in contrast wounds healed completely in wildtypes by this time (n=5 animals per genotype). Corneas immunostained for macrophages (F4/80) and neutrophils (NIMP–R14), 4, 8, and 24 hours after stromal incision wounding and exposure to LPS, showed significantly lower numbers of macrophages and neutrophils in the Lum–/– corneas compared to wildtype controls. Measurement of inflammatory cytokines in the injured corneas showed poor induction of TNFα and IL1ß in the Lum–/– mouse. We also noted a disruption in Fas–FasL mediated signaling in the Lum–/– mouse. Conclusions:Lumican is required for optimal induction of inflammatory cytokines, recruitment of inflammatory cells and efficient healing of stromal wounds. Impaired induction of inflammatory cytokines in the Lum–/– mouse may be due to disruptions in Fas–signaling in the absence of lumican.
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