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Eisuke Shimizu, Yoko Ogawa, Jingliang He, Shinji Fukuda, Kazuo Tsubota; Positive effects of oral antibiotics administration to murine graft-versus-host disease.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4952.
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Graft-versus-host disease (GVHD)-related dry eye disease is one of the most frequent complications after allogeneic hematopoietic stem cell transplantation. Dysbiosis and devastated microbiome are reported to be the important cause of autoimmune disorder. The purpose of this study is to elucidate positive and negative effects of several antibiotics administration to autoimmune-like GVHD murine model.
To obtain a mouse model of GVHD, whole bone marrow transplantation (BMT) after irradiation was conducted. The donors are 8-week-old B10.D2 male mice and the recipients are age-matched BALB/c female mice, it is allogeneic transplantation and furnishes a mouse model of GVHD (Zhang, Y. et al J Immunol. 2002). The allogeneic BMT recipients were treated perorally with either Ampicillin (APBC), Gentamicin (GM), Fradiomycin (FRM), Vancomycin (VCM), or the solvent vehicle which set to be the control group. We performed ocular examination, histological investigation, immunohistochemical examination, quantitative PCR (qPCR), and electron microscopic analysis to explore whether antibiotics administration could mitigate GVHD phenotype.
Tear break-up time was vastly higher in GM-treated group compared with the controls (6.33±2.08 vs 2.17±0.76 sec, n=8, p=0.03, Unpaired T test). In addition, tear secretion was significantly higher in the GM treated group compared with the controls (80.19±38.70 vs 21.56±9.22 %, n=8, p=0.03, rate between before and after appearance of GVHD, Unpaired T test). Histopathological assessments and immunofluorescence staining suggested that GM administration suppressed GVHD-induced inflammatory cell infiltration in colon. In addition, the results of qPCR indicate that the mRNA expression of forkhead box P3 (Foxp3) was higher in the colons treated with GM compared with the controls, which suggests regulatory T cell expression was higher in the GM-treated colons. However, other antibiotics recipients did not trace these tendencies.
This study suggests that oral GM administration alleviates inflammation caused by GVHD and therefore can be an innovative drug repositioning strategy to attenuate GVHD-related dry eye disease.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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