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Carlos A. Medina-Mendez, Alexander M. Rowe, Jared E. Knickelbein, Robert L. Hendricks; Azithromycin (azm) Treatment Increases Survival of High Risk Corneal Allotransplants. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2383.
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To test the therapeutic efficacy of AZM, a macrolide antibiotic for prolonging murine "high risk" corneal allograft survival.
Allogeneic corneas were transplanted from C57BL/6 donors to Balb/c recipients with suture-induced vascularized "high risk" corneal beds. Recipient mice were either not treated or treated with topical , oral, or topical and oral AZM. The grafts were examined for clarity and vascularization by a masked observer at least three times a week by for a period of 25 days. A score ranging from 1-4 for clarity and 1-16 for vascularization was assigned to each transplant. A corneal graft was considered rejected upon receiving two consecutive 3+ scores by a masked observer. The allospecific T cell responses were measured in draining lymph nodes 25 days post transplant based on T cell proliferation and interferon gamma production in mixed lymphocyte cultures.
The incidence of rejection in the control group (72%) was significantly reduced by AZM treatment (38% topical, 9.1% oral, 12.5% topical + oral), although corneal vascularization was not influenced. There was a trend toward a lower level of opacity in accepted corneas that received oral AZM + topical AZM compared to those receiving oral AZM alone. The allospecific T cell response was elevated in the AZM treated mice.
AZM proved effective in prolonging survival of "high risk" corneal allografts, and oral + topical appears to be somewhat more effective in reducing pathology than oral AZM alone, though this difference has not yet achieved statistical significance. While AZM’s mechanism of action remains to be defined, it does not appear to involve modulation of corneal neovascularization or the allospecific T cell response as measured at 25 days post transplant.
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