Our laboratory studies the causes of type 1 diabetes (T1D), and methods for preventing or curing disease using the non obese diabetic (NOD) mouse. Until now we have always had to cull mice to excise the pancreas to examine events in the islets, and the variation in disease progression between individual mice has meant that group sizes have to be large to estimate differences between treatments. We propose to employ a completely novel method we have developed in collaboration with the University of Glasgow for imaging of transplanted islets in the pinna of the ear, to investigate and explore the efficacy of therapeutic intervention strategies for T1D. This method permits non-invasive, in vivo longitudinal imaging of immunological events in the islets, interrogating factors such as immune infiltration and beta cell mass repeatedly in the same mouse. This will enable us to further elucidate the mechanism(s) of protection from T1D afforded by various treatments, as well as explore possibilities of combining treatment with protocols that increase endogenous beta cell mass to achieve restoration of glucose control. Our preliminary studies support our proposal and suggest that this longitudinal in vivo imaging will provide insight into key events in the islet. This new technique will allow us to gain further insight into immune mediated destruction of beta cells and mechanisms for therapeutic protection, but also be a useful tool to investigate beta cell development, differentiation and function.
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