June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Inhibition of recurrent experimental autoimmune uveitis by blockade of the receptor for advanced glycation end products (RAGE)
Author Affiliations & Notes
  • Hui Shao
    Ophthalmology, University of Louisville, Louisville, Kentucky, United States
  • Juan Yun
    Ophthalmology, University of Louisville, Louisville, Kentucky, United States
  • Tong Xiao
    Ophthalmology, University of Louisville, Louisville, Kentucky, United States
  • Yuan Zhao
    Sullivan University College of Pharmacy, Louisville, Kentucky, United States
  • Deming Sun
    Doheny Eye Institute, Los Angelos, California, United States
  • Henry J Kaplan
    Ophthalmology, University of Louisville, Louisville, Kentucky, United States
  • Footnotes
    Commercial Relationships   Hui Shao, None; Juan Yun, None; Tong Xiao, None; Yuan Zhao , None; Deming Sun, None; Henry Kaplan, None
  • Footnotes
    Support  This work was supported in part by NIH grant EY024051 and an unrestricted grant from Research to Prevent Blindness (RPB) Inc.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 563. doi:
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    • Get Citation

      Hui Shao, Juan Yun, Tong Xiao, Yuan Zhao, Deming Sun, Henry J Kaplan; Inhibition of recurrent experimental autoimmune uveitis by blockade of the receptor for advanced glycation end products (RAGE). Invest. Ophthalmol. Vis. Sci. 2017;58(8):563.

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

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Abstract

Purpose : The mechanism of recurrent autoimmune uveitis is unknown. The receptor for advanced glycation end products (RAGE) has been linked to chronic inflammation. It is able to bind ligands of AGE and some damage associated molecules such as HMGB1 and S100A8/A9. In the current study, using anti-RAGE antibody (Ab), we examined the role of RAGE in recurrent experimental autoimmune uveitis (r-EAU) induced by uveitogenic T cells.

Methods : r-EAU was induced in Lewis rats by adoptive transfer of interphotoreceptor retinoid-binding protein (IRBP) peptide R16-specific T cells. These rats were intraocularly treated with anti-RAGE Ab. Intraocular inflammation was examined by fundoscopy and histology. Proliferation, cytokine production and disease inducing ability of responder T cells from treated or non-treated rats were determined and compared.

Results : Administration of anti-RAGE Ab in r-EAU significantly reduced the severity of intraocular inflammation and the frequency of recurrence. In addition, rats treated with anti-RAGE Ab generated decreased numbers of IFN-γ+ and IL-17+ uveitogenic T cells, but increased numbers of Foxp3+ regulatory T cells. Mechanistic studies showed that the effect of the injected anti-RAGE Ab was on antigen presenting cells (APCs). Anti-RAGE Ab–treated APCs caused R16-specific T cells to lose their uveitogenic activity and acquire immunosuppressive activity, which suppressed the induction of EAU by additional pathogenic R16-specific effector T cells.

Conclusions : Ligands-RAGE axis plays an important role in r-EAU by driving uveitigenic T cell pathogenicity through APCs. Anti-RAGE Ab can protect from the development of r-EAU by inducing regulatory APCs that convert pathogenic T cells into regulatory T cells.

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

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