Effect of itraconazole on the cornea in a murine suture model and penetrating keratoplasty model

• 作者: Balamurali Ambati Eun Young Shin Hironori Uehara Yang Kyung Cho
• 来源期刊: 国际眼科杂志：英文版
• 学科: 医学
• 关键词: ITRACONAZOLE amphotericin B NEOVASCULARIZATION 接枝幸存 LYMPHANGIOGENESIS DEXAMETHASONE
• 年，卷（期）: 2017,（11）
• 页码范围: 1647-1654
• 页数: 8页
• 分类号: R77

摘要

AIM: To investigate the anti-(lymph)angiogenic and/or anti-inflammatory effect of itraconazole in a corneal suture model and penetrating keratoplasty(PK) model. METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among itraconazole, amphotericin B, dexamethasone, phosphate buffered saline(PBS) and surgery-only groups following subconjunctival injection in mice that underwent PK and corneal suture. Immunohistochemical staining and analysis were performed in each group. Real-time polymerase chain reaction(RT-PCR) was performed to quantify the expression of inflammatory cytokines(TNF-alpha, IL-6) and vascular endothelial growth factor(VEGF)-A, VEGF-C, VEGFR-2, and VEGFR-3.RESULTS: In the suture model, the itraconazole group showed less angiogenesis, less lymphangiogenesis, and less inflammatory infiltration than the PBS group(all P<0.05). The itraconazole group showed reduced expression of VEGF-A, VEGFR-2, TNF-alpha, IL-6 than the PBS group(all P<0.05). In PK model, the two-month graft survival rate was 28.57% in itraconazole group, 62.50% in dexamethasone group, 12.50% in PBS group, 0 in amphotericin B group and 0 in surgery-only group. Graft survival in the itraconazole group was higher than that in the amphotericin, PBS and surgery-only group(P=0.057, 0.096, 0.012, respectively). The itraconazole group showed less total angiogenesis and lymphangiogenesis than PBS group(all P<0.05).CONCLUSION: Itraconazole decrease neovascularization, lymphangiogenesis, and inflammation in both a corneal suture model and PK model. Itraconazole has anti-(lymph)-angiogenic and anti-inflammatory effects in addition to its intrinsic antifungal effect and is therefore an alternative treatment option in cases where steroids cannot be used.