Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.
Cornea. 2013 May;32(5):658-66. doi: 10.1097/ICO.0b013e318274a690.
To test the therapeutic efficacy of azithromycin (AZM), a macrolide antibiotic for prolonging murine "high-risk" corneal allograft survival.
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.
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.
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.
测试阿奇霉素（AZM）作为一种大环内酯类抗生素对延长小鼠“高危”角膜同种异体移植物存活时间的治疗效果。
用缝线诱导血管化的高危角膜床将 C57BL/6 供体的全组织相容性复合体错配角膜移植到 BALB/c 受体中。受体小鼠未经处理或用局部 AZM、口服 AZM 或两者联合处理。以盲法评估移植物血管化和透明度。通过流式细胞术从淋巴结中切除并分析 CD4、FoxP3 和 CD44，并通过混合淋巴细胞培养进行增殖和细胞因子产生分析来评估 T 细胞的启动。通过共聚焦显微镜评估角膜全层。
对照组（81.8%）的移植物排斥发生率通过 AZM 治疗（局部 18.2%、口服 21.7%、局部+口服 33.3%）显著降低，尽管治疗并未影响角膜血管化。在 AZM 治疗组中，移植后保留完全透明的角膜的频率更高。AZM 治疗组中降低的移植物排斥与降低的同种异体 T 细胞反应或增加的调节性 T 细胞频率无关。
AZM 通过一种尚未明确的机制有效延长高危角膜同种异体移植物的存活时间，该机制似乎不涉及角膜新生血管形成或同种异体 T 细胞启动的调节。
