May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Analysis of Herpetic Stromal Keratitis in CCR5-and/or CXCR3-Deficient Mice
Author Affiliations & Notes
  • Y. Inoue
    Department of Ophthalmology, Tottori Univ Faculty of Medicine, Yonago, Japan
  • K. Komatsu
    Department of Ophthalmology, Tottori Univ Faculty of Medicine, Yonago, Japan
  • D. Miyazaki
    Department of Ophthalmology, Tottori Univ Faculty of Medicine, Yonago, Japan
  • K. Morohoshi
    Department of Ophthalmology, Tottori Univ Faculty of Medicine, Yonago, Japan
  • C.-H. Kuo
    Department of Ophthalmology, Tottori Univ Faculty of Medicine, Yonago, Japan
  • A. Kakimaru
    Department of Ophthalmology, Tottori Univ Faculty of Medicine, Yonago, Japan
  • S. Namba
    Department of Ophthalmology, Tottori Univ Faculty of Medicine, Yonago, Japan
  • M. Haino
    Department of Molecular Preventive Medicine, Tokyo Univ School of Medicine, Tokyo, Japan
  • K. Matsushima
    Department of Molecular Preventive Medicine, Tokyo Univ School of Medicine, Tokyo, Japan
  • Footnotes
    Commercial Relationships Y. Inoue, None; K. Komatsu, None; D. Miyazaki, None; K. Morohoshi, None; C. Kuo, None; A. Kakimaru, None; S. Namba, None; M. Haino, None; K. Matsushima, None.
  • Footnotes
    Support Grand-in-Aid 15390531 for Scientific Research from the Japanese Ministry of Education, Science and Culture
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1927. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Y. Inoue, K. Komatsu, D. Miyazaki, K. Morohoshi, C.-H. Kuo, A. Kakimaru, S. Namba, M. Haino, K. Matsushima; Analysis of Herpetic Stromal Keratitis in CCR5-and/or CXCR3-Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1927. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose:: Herpetic stromal keratitis (HSK) is an immunopathological reaction resulting from herpes simplex virus type 1 (HSV-1) corneal infection. It has been reported that CD4+ cells play the most important roles among various participant cells in the pathogenesis of this disease. In this study, we have focused on two chemokine receptors, CCR5 and CXCR3, which are expressed on CD4+ cells, in mice HSK model.

Methods:: CCR5-deficient (CCR5KO), CXCR3-deficient (CXCR3KO), CCR5/CXCR3 double-deficient (DKO) and wild type (WT) mice (C57/BL6 background) were infected intracorneally with HSV-1 (strain CHR3) and examined clinically by biomicroscope. Histological and immunohistochemical evaluation was performed using cryosections of cornea. Real-time RT-PCR and RNase protection assay revealed molecular basis in this model, and virus titers were measured in excised eyes and trigeminal ganglia (TG).

Results:: HSK clinical scores in DKO mice were significantly decreased compared with WT mice. Histlogically, corneal infiltrating cells, including neutrophils and T cells (CD4+ and CD8+ cells) were significantly reduced in CCR5KO, CXCR3KO, and DKO mice. Transcript levels of immune-related cell surface marker in the eye were reduced in DKO mice. The expression of chemokine and chemokine receptor levels in cornea demonstrated significant increase of I-TAC in CCR5KO mice and decrease of MIP-1 alpha and MIP-1 beta in CXCR3KO mice compared with those of WT mice. There were no significant differences of virus titers in eyes and TG among any groups of mice except the increase in TG of DKO mice at day 5 post-infection.

Conclusions:: Collectively, the suppression of chemotaxis and activation of CD4+ Th1 cells by the lacking of CXCR3 and CCR5 caused the decrease of other infiltrating cells, resulting in the reduction of HSK without any increase of viral growth. These results suggest that the treatment of HSK by targeting chemokine receptors is one of promising ways to treat HSK.

Keywords: herpes simplex virus • keratitis • immunomodulation/immunoregulation 
×
×

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.

×