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L.P. Borges, C. Cursiefen, J.W. Streilein; Local macrophage depletion improves survival of corneal xenografts in mice by blocking antigen presentation and inhibiting hem– and lymphangiogenesis. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):601.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: BALB/c mice reject orthotopic guinea pig corneas acutely (8–12 days) by a macrophage–dependent process triggered by specific CD4+ Th1 effector cells. We wished to determine which aspect(s) of macrophage function is (are) responsible for graft rejection. Methods: At the time that guinea pig corneas were grafted orthotopically into eyes of BALB/c mice, liposomes containing clodronate or PBS were injected subconjunctivally. Groups of recipients were examined subsequently as follows: at 12 hrs grafted eyes were enucleated from euthanized mice and the corneas stained for CD11b+, GR–1+ and F4/80+ cells; at 7 days corneas of grafted eyes of euthanized mice were stained for LYVE–1 and CD31 (markers of new blood and lymph vessels); xenografts in eyes of 10 recipients were evaluated clinically via slitlamp for evidence of irreversible rejection (opacity). Results: Few F4/80+ (but many CD11b+) cells were detected in the clodronate–treated xenograft beds within 12 hrs of grafting, and few if any CD31+ and/or LYVE–1+ endothelial cells were detected in these beds at 7 days. Corneal xenografts in clodronate treated eyes displayed opacity scores indicative of rejection between 20 and 23 days post grafting. Conclusions: Elimination of recruited macrophages suppresses angiogenesis and inhibits recipient sensitization to xenoantigens on cornea grafts. Together these macrophage–inhibitory effects promote the survival of corneal xenografts significantly.
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