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Title: Immunoregulatory strategies in corneal transplantation and dry eye disease
Author: Foulsham, William
ISNI:       0000 0004 8508 3895
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2020
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Despite substantial advances in our understanding of the cellular and molecular factors that regulate immune homeostasis at the ocular surface and anterior segment, important questions remain. In this thesis I present investigations of two phases of the adaptive immune response - the antigen recognition phase, and the final memory phase. In my experiments I employ murine models of corneal transplantation and dry eye disease. Specifically, I investigate how the activation of antigen-presenting cells is modulated by purinergic signaling and by mesenchymal stem cells in a model of corneal transplantation. Furthermore, I investigate how IL-15 signaling regulates the memory T helper 17 cell pool in age-related dry eye disease. In addition to providing useful models to investigate immunoregulation in the eye, studies of corneal transplantation and dry eye disease are of high translational potential. Corneal transplantation is the most common form of tissue grafting performed worldwide. Despite high success rates in low-risk recipients, failure rates exceed 50% in patients with a history of graft rejection, or with vascularized and inflamed host beds. Dry eye disease is an extremely common chronic condition of the ocular surface, with prevalence estimated to be more than 10% for ages greater than 50 years. Dry eye disease significantly impairs quality of life and is associated with a substantial socioeconomic burden. Accordingly, there is an unmet clinical need for novel therapeutic strategies to improve corneal allograft survival and treat dry eye disease. The data presented in this thesis indicate that both the purinergic receptor antagonist oxidized adenosine triphosphate and mesenchymal stem cell-derived hepatocyte growth factor promote corneal allograft survival by regulating antigen-presenting cell maturation. In addition, the data presented indicate that targeting interleukin-15 signaling is an effective strategy to deplete the memory T helper 17 pool in aged mice and reduce the severity of age-related dry eye disease.
Supervisor: Calder, V. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available