June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Umbilical mesenchymal stem cell transplantation for dry eye in the mouse model
Author Affiliations & Notes
  • Hongshan Liu
    Ophthalmology, University of Cincinnati, Cincinnati, OH
  • Yujin Zhang
    Ophthalmology, University of Cincinnati, Cincinnati, OH
  • Yong Yuan
    Ophthalmology, University of Cincinnati, Cincinnati, OH
  • Jianhua Zhang
    Ophthalmology, University of Cincinnati, Cincinnati, OH
  • Chia-yang Liu
    Ophthalmology, University of Cincinnati, Cincinnati, OH
  • Winston Kao
    Ophthalmology, University of Cincinnati, Cincinnati, OH
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2192. doi:
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      Hongshan Liu, Yujin Zhang, Yong Yuan, Jianhua Zhang, Chia-yang Liu, Winston Kao; Umbilical mesenchymal stem cell transplantation for dry eye in the mouse model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2192.

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

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Abstract

Purpose: Dry eye is a multifactorial disease of the tear and ocular surface that is characterized by T cell infiltration; and so far, there is no effective long-term cure for dry eye. We previously reported a bi-transgenic dry eye mouse model of Krt12rtTA/tet-O-hIL-1b (IL-1β driven by keratin 12 promoter) mimicking human dry eye after doxycycline induction. In present study, we used this mouse model to test the efficacy of umbilical mesenchymal stem cell (UMSC) transplantation in treating dry eye.

Methods: UMSCs were transplanted into the corneal stroma and subconjunctiva of bitransgenic mice following doxycycline-induction for 4 weeks and then removal of doxycycline for 12 weeks. In vivo, stereomicroscopy and HRT-II confocal microscopy were performed to evaluate the pathological change of ocular surface tissue at different time points. Mice were sacrificed and ocular tissues harvested were subjected to histology and immunofluorescence staining to identify inflammatory and immune cell types and expression of anti-inflammatory cytokines by UMSC.

Results: HRT-II examination revealed that the intensity of corneal haze was significantly decreased one week after UMSC transplantation in comparison with un-treated corneas exhibiting progressive corneal haze with times. Immunostaining with anti-CD4 antibody showed that the infiltration of CD4+ cells was reduced in the treated eyes. Immunostaining indicates that transplanted UMSCs are positive for interleukin-1 receptor antagonist (IL-1RA), but not IDO, PGE2, TSG-6, TSG-14, iNOS, and IL-10. To investigate whether secreted IL-1RA is related to IL-1β stimulation, UMSCs were incubated in 10 ng/ml human IL-1β/α-MEM medium and the results revealed an up-regulated level of IL-1RA expression.

Conclusions: MSC transplantation may be a novel therapeutic strategy for dry eye by suppressing T-cell infiltration into the ocular surface tissues of dry eye.

Keywords: 486 cornea: tears/tear film/dry eye • 721 stem cells • 555 immunomodulation/immunoregulation  
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