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Eisuke Shimizu, Yoko Ogawa, HIROYUKI YAZU, Masaki Fukui, Shinji Fukuda, Yutaka Kawakami, Kazuo Tsubota; A novel and effective oral antibiotics treatment to the graft-versus-host disease model mouse.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6727.
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© ARVO (1962-2015); The Authors (2016-present)
Graft-versus-host disease (GVHD)-related dry eye disease (DED) is one of the most frequent and lethal complications after allogeneic hematopoietic stem cell transplantation. Dysbiosis of the gut microbiome are reported to be the important piece in several autoimmune disorders. We reported the positive effect of oral antibiotics treatment to GVHD murine model (ARVO 2018) as its pathology is said to be the autoimmune-like disorder. Our purpose is to confirm the reproducibility and elucidate the effective cause of the oral antibiotics treatment to the GVHD-related DED model mouse.
We have created the GVHD-related DED model mouse using established in the established manner (Zhang, Y. et al J Immunol. 2002). The recipients were treated orally by Ampicillin (APBC), Gentamicin (GM), Fradiomycin (FRM), Vancomycin (VCM), or the solvent vehicle. We observed several phenotypes as ocular examination, systemic evaluation, and microbiome analysis by 16s rRNA gene sequencing.
Ocular phenotypes as well as systemic phenotypes had significant improvement in antibiotics administrated group (Clinical GVHD Severity Score, tear secretion, tear firm breakup time, expression of Foxp3 in colon, Foxp3 positive cell count in Flow cytometry). These results correlated with the previous results. Furthermore, in the microbiome analysis, bacterial genus Bifidobacterium was 146 times higher in the GM administration group compared to GVHD model mouse (P<0.05. Student's t-test), which had best ocular and systemic phenotype among all antibiotics administration group. We has similar correalation between the better GVHD phenotype and the amout of the bacterial genus Bifidobacterium.
We confirmed the reproducibility of the oral antibiotics treatment to the GVHD-related DED model mouse. Also, constructed the possible hypothesis that the change in gut microbiome by oral antibiotics administration alleviates inflammation caused by GVHD and therefore can be an innovative drug repositioning strategy to attenuate GVHD-related dry eye disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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