July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Topical Leukocyte Function-Associated Antigen-1 (LFA-1) Antagonist Treatment (Lifitegrast) Suggest that Immune Synapsis and T cell Adhesion in Limbal Vessels is affected during DED
Author Affiliations & Notes
  • Gustavo Ortiz
    Hamrah Lab Location: Tupper 2nd floor, Center for Translational Ocular Immunology, Boston, Massachusetts, United States
  • Victor German Sendra
    Pathology Department, Universidad de Buenos Aires, Buenos Aires, Buenos Aires, Argentina
  • Arsia Jamali
    Hamrah Lab Location: Tupper 2nd floor, Center for Translational Ocular Immunology, Boston, Massachusetts, United States
  • Pedram Hamrah
    Hamrah Lab Location: Tupper 2nd floor, Center for Translational Ocular Immunology, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Gustavo Ortiz, Shire (F); Victor Sendra, None; Arsia Jamali, None; Pedram Hamrah, Allergan (C), Allergan (S), Bausch & Lomb (C), Santen (C), Shire (F), Shire (C), Shire (S)
  • Footnotes
    Support  Shire
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2821. doi:
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      Gustavo Ortiz, Victor German Sendra, Arsia Jamali, Pedram Hamrah; Topical Leukocyte Function-Associated Antigen-1 (LFA-1) Antagonist Treatment (Lifitegrast) Suggest that Immune Synapsis and T cell Adhesion in Limbal Vessels is affected during DED. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2821.

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

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Abstract

Purpose : The leukocyte function-associated antigen-1 (LFA-1) binds to the intercellular adhesion molecule (ICAM) family, with its principal ligand being ICAM-1. ICAM-1/LFA-1 interaction is essential for T-cell activation as well as for migration of T-cells to target tissues.The purpose of this study was to assess if LFA-1 antagonist Lifitegrast can modulate T cell activation in the dLNs, subsequently affecting T cell migration to the ocular surface during DED

Methods : DED was induced in 6-8 week old wild-type mice by exposure to the controlled environmental chamber and subcutaneous injections of scopolamine. Mice were treated with topical Lifitegrast (or normal saline [NS] control) 3 times daily. To asses clinical DED severity, corneal fluorescein score (CFS) was evaluated in both groups. Corneal T cells were quantified by flow cytometry of single cell suspensions at days 10, 15 and 21. T cells from NS-treated and Lifitegrast-treated DED mice were used as donors for adoptive transfer experiments to NS-treated DED mice (recipients). Protein levels of interleukin (IL)-1b, IL-6, IL-10, IL-17, interferon (IFN)-g, and tumor necrosis factor (TNF)-awere measured in tear samples using Bio-plex

Results : Lifitegrast-treatment of DED mice resulted in significant reduction of CFS and in reduced corneal T cells as compared to the NS group by flow cytometry at days 15 and 21 (p<0.05). Limbal vascular sticking efficacy (adhesion) of donor T cells from a DED mice was increased in recipient DED mice at days 15 (62±12)% and 21 (54±6)%. Donor T cells from Lifitegrast-treated (9 ±4)% were comparable to T cells from naïve donor (5±3)% mice (p<0.001). The cytokines IFN-g (75±12) pg/ml, (52±14) pg/ml, (47±15) pg/ml and IL-17 (40±14) pg/ml, (37±9) pg/ml, (69±10) pg/ml were increased, in tears of NS-treated DED mice at days 10, 15 and 21 respectively. While they were reduced in Lifitegrast-treated DED mice (22 ±8) pg/ml, (18±12) pg/ml, (12±8) pg/ml and (10±4) pg/ml, (15±9) pg/ml, (18±8) pg/ml for IFN-g and IL-17 respectively (p<0.05)

Conclusions : Lifitegrast treatment results in decreased corneal T cell migration and pro-inflammatory tear cytokines in DED. Adoptive transfer experiments suggest that topical Lifitegrast may be reaching dLN and potentially affecting T cell activation and subsequent T cell adhesion to limbal vessels.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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