September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
PD Ligand Blockade Decreases IRBP-induced Uveitis in Mice
Author Affiliations & Notes
  • Negin Ashki
    Ophthalmology, University of California Los Angeles, Los Angeles, California, United States
  • Ann M Chan
    Ophthalmology, University of California Los Angeles, Los Angeles, California, United States
  • Yu Qin
    Ophthalmology, University of California Los Angeles, Los Angeles, California, United States
  • Ralph D Levinson
    Ophthalmology, University of California Los Angeles, Los Angeles, California, United States
  • Lynn K Gordon
    Ophthalmology, University of California Los Angeles, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Negin Ashki, None; Ann Chan, None; Yu Qin, None; Ralph Levinson, None; Lynn Gordon, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1883. doi:
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    • Get Citation

      Negin Ashki, Ann M Chan, Yu Qin, Ralph D Levinson, Lynn K Gordon; PD Ligand Blockade Decreases IRBP-induced Uveitis in Mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1883.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Uveitis is a potentially blinding, immune mediated, intraocular inflammatory disease. Although programmed death-1 (PD-1) binding to its two ligands is believed to down-regulate autoimmunity, our previous studies observed a significant and paradoxical decrease in uveitis susceptibility in mice that lacked PD-ligands. To further investigate these findings, we tested the hypothesis that PD-L blockade using an antibody against PD-L1 would decrease susceptibility to uveitis in animal models of experimental autoimmune uveitis (EAU).

Methods : Uveitis was induced in C57Bl/6 and B10. RIII mice using the appropriate IRBP peptide according to published protocols. All experiments were carried out in strict accordance with ARVO guidelines and the Guide for the Care and Use of Laboratory Animals. Mice were treated with either 10mg/kg of anti-PD-L1 antibody (BioXCell) twice a week for three weeks (C57BI/6), 10 mg/kg of anti-PD-L1 antibody once a week for two weeks (B10.RIII) or 10mg/kg of IgG control at the same frequency as the anti-PD-L1 antibody. A masked clinical assessment by funduscopic examinations was done every day for 3 weeks after the immunization. The severity of the retinal inflammation was graded on a four-point scale. At 3 weeks following immunization, the eyes were enucleated, fixed tissues were stained, and the histological severity graded by masked observers using a published scale.

Results : We found significant abrogation of uveitis in both C57BI/6 and B10.RIII animals. The percent of C57BI/6 mice that failed to developed uveitis following treatment with anti-PD-L1 antibody was 85%, whereas 100% of animals in the IgG control or no treatment group developed intraocular inflammation (P<0.0001). Similarly, 75% of B10.RIII were protected against uveitis following treatment with anti-PD-L1 antibody, whereas 100% of animals developed uveitis in both IgG control and EAU groups (P<0.0014).

Conclusions : The decrease in uveitis susceptibility following treatment with anti-PD-L1 antibody confirmed our previous findings. First, this observation may lead to a new understanding of uveitis pathogenesis in terms of understanding how the PD-1 system affects uveitis susceptibility. Second, these results suggest the potential for the PD-1 as a possible therapeutic target in control of ocular inflammation.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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