Cornea · 2013
Azithromycin treatment increases survival of high-risk corneal allotransplants.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Medina Carlos A, Rowe Alexander M, Yun Hongmin, Knickelbein Jared E, Lathrop Kira L, Hendricks Robert L
Аннотация
PURPOSE: To test the therapeutic efficacy of azithromycin (AZM), a macrolide antibiotic for prolonging murine "high-risk" corneal allograft survival.
METHODS: Fully major histocompatibility complex-mismatched 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 AZM, oral AZM, or both. Evaluation of graft vascularization and clarity was performed in a masked fashion. Lymph nodes were excised and analyzed for CD4, FoxP3, and CD44 by flow cytometry, and for T-cell priming by proliferation and cytokine production in mixed lymphocyte cultures. Corneal whole mounts were evaluated by confocal microscopy.
RESULTS: The incidence of graft rejection in the control group (81.8%) was significantly reduced by AZM treatment (18.2% topical, 21.7% oral, 33.3% topical + oral), although corneal vascularization was not affected by the treatment. The frequency of corneas that retained complete clarity after transplantation was higher in the AZM-treated groups. Reduced graft rejection in the AZM-treated groups was not associated with a reduced allospecific T-cell response or increased frequency of regulatory T cells.
CONCLUSIONS: AZM is effective in prolonging survival of high-risk corneal allografts by an as yet undefined mechanism that does not seem to involve modulation of corneal neovascularization or allospecific T-cell priming.
METHODS: Fully major histocompatibility complex-mismatched 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 AZM, oral AZM, or both. Evaluation of graft vascularization and clarity was performed in a masked fashion. Lymph nodes were excised and analyzed for CD4, FoxP3, and CD44 by flow cytometry, and for T-cell priming by proliferation and cytokine production in mixed lymphocyte cultures. Corneal whole mounts were evaluated by confocal microscopy.
RESULTS: The incidence of graft rejection in the control group (81.8%) was significantly reduced by AZM treatment (18.2% topical, 21.7% oral, 33.3% topical + oral), although corneal vascularization was not affected by the treatment. The frequency of corneas that retained complete clarity after transplantation was higher in the AZM-treated groups. Reduced graft rejection in the AZM-treated groups was not associated with a reduced allospecific T-cell response or increased frequency of regulatory T cells.
CONCLUSIONS: AZM is effective in prolonging survival of high-risk corneal allografts by an as yet undefined mechanism that does not seem to involve modulation of corneal neovascularization or allospecific T-cell priming.
Предметные рубрики MeSH
AnimalsAnti-Bacterial AgentsAzithromycinCD4 AntigensCorneal TransplantationCytokinesFlow CytometryForkhead Transcription FactorsGraft RejectionGraft SurvivalHyaluronan ReceptorsLymph NodesLymphocyte Culture Test, MixedMiceMice, Inbred BALB CMice, Inbred C57BLMicroscopy, ConfocalT-LymphocytesTransplantation, HomologousTreatment Outcome