Effects of VLA-4 Integrin Inhibitor on Leucocyte Subset Migration in Experimental Autoimmune Uveitis
Purpose
VLA-4 integrin primarily affects leukocyte adhesion and trafficking. This study investigated its role in experimental autoimmune uveitis (EAU).
Methods
Interphotoreceptor retinoid binding protein induced EAU mice model was used. Topical VLA-4 inhibitor (GW559090) (10mg/ml and 30mg/ml) was given preventively and therapeutically. Clinical severity was evaluated at peak disease. T cell subsets within the eye were investigated by immunohistochemistry and immunofluorescence staining. Sub-populations of leucocytes in blood, eye and lymph nodes were analysed with flow cytometry.
Results
opical GW559090 reduced EAU severity (P < 0.01) therapeutically and preventively, by reducing CD45+ leucocytes in the retinal tissues (P < 0.05), but not affecting retinal structure. The Th17 cells were reduced (each P ≤ 0.001), and the Th1 cells increased (each P ≤ 0.02) only locally. CD11b+CD64+ monocytes increased in the eye by GW559090 treatment. A decrease in CD11b+ dendritic cells was observed locally and systemically (each P ≤ 0.001).
Conclusion
VLA-4 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. VLA-4 integrin-directed inhibition could be clinically relevant in Th17-dominant cases of uveitis.
Conflict of interest
No
Author 1
Last name
CHEN
Initials of first name(s)
YH
Department
UCL institute of Ophthalmology, University College London
City
London
Country
United Kingdom
Author 2
Last name
Eskandarpour
Initials of first name(s)
M
Department
UCL institute of Ophthalmology, University College London
City
London
Country
United Kingdom
Author 3
Last name
Lightman
Initials of first name(s)
Sue
Department
Moorfields Eye Hospital, London, United Kingdom.
City
London
Country
United Kingdom
Author 4
Last name
Calder
Initials of first name(s)
V
Department
UCL institute of Ophthalmology, University College London
City
London
Country
United Kingdom
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