Reduction of use of experimental mice in type 1 diabetes research through non-invasive, in vivo longitudinal imaging

Our laboratory studies Type 1 Diabetes (T1D), which is an autoimmune disease caused by an attack of the body's own immune system against the insulin producing beta cells in the pancreas. Once these cells are destroyed, patients need to inject insulin in order to take up glucose. Manual glucose monitoring and insulin injection cannot balance blood glucose levels as well as endogenous production, and complications arising from poor glucose control are common. The aim of our research is to discover a cure for this disease.

As T1D is mediated by the immune system, and many of the processes involved are too complex to be replicated in an in vitro system, a lot of our work therefore requires use of experimental mice. As disease progression is not uniform even in the T1D prone non-obese diabetic (NOD) mouse strain, large groups of mice need to be assessed to determine if a treatment reduces immune infiltration in the islets, or if it changes the proportions of different types of immune cells. As the pancreas is situated within the abdominal cavity the mice have to be culled to access it, meaning that for every time point studied a fresh group of mice has to be used.

Our proposal describes the use of a completely novel method for investigating immune infiltration into islets transplanted into the pinna of the ear. This method allows non-invasive and repeated investigation of the same islets at different time points. The fact that the same individual can be measured before and after any treatment removes the need for large group sizes, and as the imaging is non invasive the same individual can be measured at several time points, reducing the number of groups needed. We believe that this novel technique will allow us to collect better quality data using significantly fewer experimental animals.

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.

We believe that our proposed work will establish a method for investigating events in the islets that will:
1. reduce the number of mice required (we estimate it could reduce the number used in diabetes studies by almost 10,000 mice)
2. allow collection of previously unattainable data