June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Fas-dependent release of high-mobility group protein B1 (HMGB1) in the eye is critical for the development of experimental autoimmune uveitis (EAU) initiated by uveitogenic T cells
Author Affiliations & Notes
  • Guomin Jiang
    Department of Ophthalmology, University of Louisville, Louisville, KY
  • Amir Hajrasouliha
    Department of Ophthalmology, University of Louisville, Louisville, KY
  • Henry Kaplan
    Department of Ophthalmology, University of Louisville, Louisville, KY
  • Hui Shao
    Department of Ophthalmology, University of Louisville, Louisville, KY
  • Footnotes
    Commercial Relationships Guomin Jiang, None; Amir Hajrasouliha, None; Henry Kaplan, None; Hui Shao, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2028. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Guomin Jiang, Amir Hajrasouliha, Henry Kaplan, Hui Shao; Fas-dependent release of high-mobility group protein B1 (HMGB1) in the eye is critical for the development of experimental autoimmune uveitis (EAU) initiated by uveitogenic T cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2028.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: We have previously reported that HMGB1, an important member of damage-associated molecular patterns (DAMPs), is an early and critical mediator in the eye in response to transferred uveitogenic T cells and that transfer of uveitogenic T cells into Fas deficient (lpr) mice did not induce HMGB1 release by retinal tissue cells nor result in intraocular inflammation. In this study, we wanted to test if HMGB1 release in the eye is Fas-dependent.

Methods: : Retinal explants from Fas-deficient (Faslpr) and wild-type (wt) C57BL/6 (B6) mice were cultured with a Fas receptor agonist (Jo2 Ab) or interphotoreceptor retinoid-binding protein (IRBP) 1-20 peptide-specific T cells, and then the level of HMGB1 in culture supernatants were detected by ELISA. In addition, uveitis was evaluated after IRBP-specific T cell transfer into both Faslpr mice intra-vitreous injected with recombinant HMGB1and in wt B6 mice intra-vitreous injected with a Fas signaling antagonist (Met12).

Results: Compared to Faslpr retinal explants, high level of HMGB1 was detected in the culture supernatants of wt retinal explants cocultured with either IRBP-specific T cells or Jo2 Ab for 2 and 4 hours. The increased HMGB1 release was suppressed by Fas signaling pathway inhibitor Met12. Moreover, IRBP-specific T cells induced uveitis in Faslpr mice intravitreously injected with HMGB1, whereas, uveitis induced by IRBP-specific T cells in wt B6 mice was attenuated by Met12 treatment.

Conclusions: : Except the fact that Fas could mediate apoptotic cell death, we have found that Fas signaling is also involved in HMGB1 secretion from intact retinal cells in response to uveitogenic T cells. Blockade of Fas signaling pathway reduced HMGB1 release, thus, suppressing the development of uveitis. Met12, a Fas antagonist, might be a potential alternative for the treatment of autoimmune uveitis in man.

Keywords: 432 autoimmune disease • 557 inflammation • 451 chorioretinitis  
×
×

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.

×