July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Effects of α4β1 Integrin Inhibitor on Leucocyte Subset Migration in Experimental Autoimmune Uveitis
Author Affiliations & Notes
  • Yi hsing Chen
    Institute of Ophthalmology, University College London, London, United Kingdom
    Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
  • Malihe Eskandarpour
    Institute of Ophthalmology, University College London, London, United Kingdom
  • Grazyna Galatowicz
    Institute of Ophthalmology, University College London, London, United Kingdom
  • Mahid Chaudhry
    Institute of Ophthalmology, University College London, London, United Kingdom
  • Xiaozhe Zhang
    Institute of Ophthalmology, University College London, London, United Kingdom
  • Susan Lightman
    Institute of Ophthalmology, University College London, London, United Kingdom
    Moorfields Eye Hospital, London, United Kingdom
  • Virginia Calder
    Institute of Ophthalmology, University College London, London, United Kingdom
  • Footnotes
    Commercial Relationships   Yi hsing Chen, None; Malihe Eskandarpour, None; Grazyna Galatowicz, None; Mahid Chaudhry, None; Xiaozhe Zhang, None; Susan Lightman, None; Virginia Calder, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2541. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Yi hsing Chen, Malihe Eskandarpour, Grazyna Galatowicz, Mahid Chaudhry, Xiaozhe Zhang, Susan Lightman, Virginia Calder; Effects of α4β1 Integrin Inhibitor on Leucocyte Subset Migration in Experimental Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2541.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : α4β1 integrin plays a cardinal role in leukocyte adhesion and trafficking. This study investigated an α4β1 integrin inhibitor (GW559090) on leucocyte migration in mouse CD4+T cell-mediated models of experimental autoimmune uveitis (EAU).

Methods : Female B10.RIII or C57/B6 mice (aged 6-8 weeks; n=6-8 mice per group), were immunized with interphotoreceptor retinoid-binding protein and Bordetella pertussis toxin for EAU. Topical GW559090 at 10mg/ml or 30mg/ml was given twice daily at afferent or efferent phase and compared to vehicle or 0.1% dexamethasone eye drops (DEX group) controls. Mice were sacrificed at peak disease for clinical, histological and flow cytometry evaluation. The T cell subsets present within the eye were investigated by immunohistochemistry and 4-colour immunofluorescence staining. The different populations of leucocytes in blood, eye and lymph nodes were analysed with flow cytometry.

Results : There was a significant reduction in clinical and histological scores in the 10mg/ml and 30mg/ml GW559090, and DEX treated groups as compared to vehicle controls given at afferent or efferent phase. There was a decrease in CD45+ leucocytes in the retinal tissues in all treated groups (P < 0.05), but no effects on the retinal structure. The cell number of CD4+ T cells did not differ by flow cytometric analysis. By immunofluorescent and flow cytometric staining, the population of the Th17 cells reduced (each P ≤ 0.001), and the Th1 cells increased (each P ≤ 0.02) in the treated eyes but not systemically. There was a significant increase in the CD11b+CD64+ macrophages in the eye in the 10mg/ml and 30mg/ml treated group (P < 0.001 and P = 0.03), and the CD11b+CD64+ activated monocytes in the blood (P = 0.01) in the 10mg/ml treated group. Furthermore, a decrease in CD11b+ dendritic cells was observed in the eye and the peripheral blood in the 10mg/ml and 30mg/ml treated groups (each P ≤ 0.001). However, there was no such effect on the DEX group.

Conclusions : α4β1 integrin inhibitor may exert a modulatory effect in EAU by selectively blocking Th17 cell migration across the blood-retinal barrier without affecting systemic T cell subsets. α4β1 integrin-directed inhibition could be clinically relevant in Th17-dominant cases of uveitis.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

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.

×