June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Leukocyte Function-Associated Antigen-1 (LFA-1) Antagonist Lifitegrast Prevents Corneal Recruitment of Effector T cells (Th1) by Modulating CXCR3 and CCR4 expression During Dry Eye Disease (DED)
Author Affiliations & Notes
  • Victor G. Sendra
    ophthalmology, Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Flavia L. Barbosa
    ophthalmology, Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Deshea L Harris
    ophthalmology, Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Pedram Hamrah
    ophthalmology, Center for Translational Ocular Immunology, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States
    Ophthalmology, Cornea Service, New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Victor Sendra None; Flavia Barbosa None; Deshea Harris None; Pedram Hamrah Noveome, Santen, Novartis, Oysterpoint Pharma, Clemenia, Novaliq, Kala Pharmaceuticals, Dompe, Code C (Consultant/Contractor), Novartis, Oyster point, Dompe, Code S (non-remunerative)
  • Footnotes
    Support  Novartis Pharmaceuticals Corporation
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 893 – A0257. doi:
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    • Get Citation

      Victor G. Sendra, Flavia L. Barbosa, Deshea L Harris, Pedram Hamrah; Leukocyte Function-Associated Antigen-1 (LFA-1) Antagonist Lifitegrast Prevents Corneal Recruitment of Effector T cells (Th1) by Modulating CXCR3 and CCR4 expression During Dry Eye Disease (DED). Invest. Ophthalmol. Vis. Sci. 2022;63(7):893 – A0257.

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

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Abstract

Purpose : The interaction of ICAM-1/LFA-1 is essential for T cell activation and migration. lntravascular ICAM-1 has been shown to be upregulated during corneal inflammation, such as in dry eye disease (DED). The purpose of this study was to assess if LFA-1 antagonist Lifitegrast can reduce CD4+ T cell migration to the cornea by modulating the expression of chemokine receptors during DED

Methods : DED was induced in 6–8 week-old mice by exposure to the controlled environment chamber and subcutaneous injections of scopolamine. Mice were treated with topical Lifitegrast (or normal saline [NS] control) 3 times daily. Fifteen days later, DED severity was assessed with corneal fluorescein score (CFS) and T cells were quantified by flow cytometry (FC) of corneal single cells for the cytokines IFN-γ (Th1) or IL-17A (Th17). Expression of chemokine receptors on T cells from local draining lymph nodes (dLNs) were assessed by qRT-PCR and FC. CD4+ T cells from DED mice treated with Lifitegrast or NS were sorted and adoptively transferred to RAG knockout (KO) mice. Five days later, DED severity was assessed and T cells were quantified in pooled corneas and dLNs by FC

Results : CFS and tear secretion were significantly increased at day 15 in DED mice treated with Lifitegrast, compared to DED mice treated with NS (p <0.001). Lifitegrast treatment resulted in reduction of CD4+ T cell recruitment (Th1) to the cornea by FC(P<0.05) with reduction of corneal IFN-γ and TNF-α compared to DED mice treated with NS. CD4+ T cells from dLNs showed reduction on the expression of chemokine receptors CXCR3 and CCR4 by FC in DED-Lifitegrast vs. NS-treated controls mice (p<0.05). Interestingly, adoptive transfer of CD4+ T cells from DED mice treated with Lifitegrast resulted in significant reduction of CFS and improved tear secretion (p<0.05) with reduction of T cells (Th1) recruitment into the cornea (17% vs. 44%) but no changes in the dLN compared to NS-treated controls

Conclusions : Lifitegrast treatment reduces CFS and improves tear secretion in DED mice, and resulted in significant reduction in corneal effector Th1 cell recruitment and reduction in pro-inflammatory cytokines. Lifitegrast treatment may mediate DED by inhibiting corneal T cell migration through the modulation of CXCR3 and CCR4 expression on CD4+ T cells in dLNs

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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