June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Attenuation of Murine Lacrimal Gland Chronic Graft-Versus-Host Disease by Oral Injection of Tranilast
Author Affiliations & Notes
  • Eisuke Shimizu
    Ophthalmology, Keio University, Shinjuku-ku, Japan
  • Shin Mukai
    Ophthalmology, Keio University, Shinjuku-ku, Japan
  • Yoko Ogawa
    Ophthalmology, Keio University, Shinjuku-ku, Japan
  • Kazuo Tsubota
    Ophthalmology, Keio University, Shinjuku-ku, Japan
  • Footnotes
    Commercial Relationships   Eisuke Shimizu, None; Shin Mukai, None; Yoko Ogawa, None; Kazuo Tsubota, None
  • Footnotes
    Support  Japanese Ministry of Education, Science, Sports and Culture,
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4726. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Eisuke Shimizu, Shin Mukai, Yoko Ogawa, Kazuo Tsubota; Attenuation of Murine Lacrimal Gland Chronic Graft-Versus-Host Disease by Oral Injection of Tranilast. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4726.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Graft-versus-host disease (GVHD)-related dry eye disease is one of the most frequent complications after allogeneic hematopoietic stem cell transplantation. Tranilast was synthesized for the first time in Japan and then approved for medical use. Over the last decades, this molecule has been utilized to treat asthma, atopic dermatitis and keloid. We have shown a significant role of fibroblasts in cGVHD induced pathogenic fibrosis including the epithelial mesenchymal transition (EMT) in lacrimal gland affected by cGVHD. Using cell-based screening methods, tranilast was found to have a potential to suppress EMT in vitro. The purpose of this study is to investigate whether tranilast is capable of mitigating inflammation, fibrosis and oxidative stress in lacrimal gland disordered by cGVHD.

Methods : Whole bone marrow transplantation (BMT) was conducted in order to obtain a mouse model of cGVHD. In the case where the donors are B10.D2 mice and the recipients are BALB/c mice, it is allogeneic transplantation and furnishes a mouse model of cGVHD (Zhang, Y. et al J Immunol. 2002). The allogeneic BMT recipients were treated with tranilast or the solvent-vehicle by oral or intraperitoneal injection. We performed (1) histological investigation, (2) immunohistochemical examination, (3) quantitative PCR (qPCR), (4) immunoblot assays and (5) electron microscopic analysis to explore whether oral or intraperitoneal injection of tranilast could mitigate cGVHD in lacrimal glands.

Results : Histopathological assessments and immunofluorescence staining suggest that oral or intraperitoneal injection of tranilast suppressed cGVHD-induced, inflammatory cell infiltration, fibrosis and oxidative stress in lacrimal glands. In addition, the results of immunoblot analysis and qPCR indicate that the protein or mRNA expression of NF-kB, CXCL9, TGF-b, and thioredoxin interaction protein (TXNIP) was vastly lower in the lacrimal glands treated with TL compared with those treated with the solvent-vehicle. As indicated by our data, oral injection of tranilast can repress lacrimal gland cGVHD in a more effective manner than intraperitoneal injection.

Conclusions : This study suggests that oral administration of tranilast alleviates inflammation and fibrosis caused by ocular cGVHD and therefore can be a promising therapeutic intervention to attenuate cGVHD related dry eye disease.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×