Citation:Cho YK,Shin EY,Uehara H,Ambati B.Effect of itraconazole on the cornea in a murine suture model and penetrating keratoplasty model.Int J Ophthalmol 2017;10(11):1647-1654,doi:10.18240/ijo.2017.11.03
Effect of itraconazole on the cornea in a murine suture model and penetrating keratoplasty model
Received:May 19, 2017  Revised:August 24, 2017
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DOI:10.18240/ijo.2017.11.03
Key Words:itraconazole  amphotericin B  neovascularization  graft survival  lymphangiogenesis  dexamethasone
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Yang Kyung Cho Department of Ophthalmology, St.Vincent’s Hospital, College of Medicine, the Catholic University of Korea, 93 Ji-Dong, Paldal-Gu, Suwon, Gyeonggi-Do 16247, Korea
Eun Young Shin Research Institute of Medical Science, St.Vincent's Hospital, the Catholic University of Korea, 93 Ji-Dong, Paldal-Gu, Suwon, Gyeonggi-Do 16247, Korea
Hironori Uehara Department of Ophthalmology, School of Medicine, University of Utah, Salt Lake City, Utah 84132, USA
Balamurali Ambati Department of Ophthalmology, School of Medicine, University of Utah, Salt Lake City, Utah 84132, USA
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Abstract:
      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.

PMC FullText Html:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686361/
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