Chen, Yi-Hsing; (2020) The role of α4β1 integrin in leukocyte infiltration in inflammatory retinal disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis focuses on clinical manifestations with effect of a specific corticosteroid eyedrop in a paediatric cohort of uveitis, transportation of leukocytes in an experimental model of autoimmune uveitis (EAU), and a specific T cell population, the Th17/Th1 cell, and its role in EAU. Chapter 1 outlines the epidemiology, importance of uveitis and discusses the evidence of the immune cells, CD4+ T cell subsets and myeloid cells in the pathogenesis of uveitis. In addition, the crucial roles of adhesion molecules are reviewed. Chapter 2 outlines the materials and methods used in the following chapters. Results are described in Chapters 3, 4 and 5. Chapter 3 explores the use of rimexolone (Vexol) eyedrops in a cohort of paediatric uveitis patients, and the associated risk factors for flare ups. I discovered that Vexol resulted in moderate control for anterior uveitis in paediatric patients and reduced the risk to flare-ups. Chapter 4 investigates leukocyte subtypes involved in crossing the blood-retinal-barrier (BRB) using in vivo and in vitro models by an α4β1 integrin small molecule inhibitor. I discovered that Th17 cells in particular were affected in their adhesion ability by an α4β1 integrin small molecule inhibitor. Chapter 5 describes the novel results of a functionally distinct CD4+ T cell subset, the Th17/Th1 cell (IFNγ+IL-17A+), and its response to corticosteroids in EAU and in in vitro studies. Chapter 6 draws together the findings from the thesis and discusses limitations and future work.

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