Date(s) - 06/23/2014
Type 1 diabetes is a chronic disease commonly diagnosed in children and young adults. Although contributing to approximately only 5-10% of diabetic patients in the world, the prevalence of this disease is increasing including in countries that originally showed negligible incidence rates. In spite of vast research going into understanding the disease and subsequently developing therapeutic solutions, the pathogenesis of this disease, to a great extent, still remains vague. A large percentage of this issue may be attributed to the fact that majority of the research in type 1 diabetes is performed on animal models. With recent studies establishing dissimilarities between rodent and human pancreas, a necessity to acquire relevant information regarding the disease from human tissues has been established.
Owing to the pronounced heterogeneity in the histopathological changes observed during the progression of type 1 diabetes in human pancreas, understanding the pathogenesis of the disease is largely constrained while using conventional immunohistochemical techniques. Additionally, due to the heterogeneous nature of the deviations, even within a small region of the pancreas, relevant data may be lost by analyzing thin sections of the tissue. This also results in a considerable amount of tissue loss which is highly undesirable, bearing in mind the scarce availability of human specimens for research. Optical clearing of tissues to permit three- dimensional analysis was investigated and complete three- dimensional models of pancreatic tissue blocks, with focus on islets were constructed using confocal microscopy. Furthermore, we investigated the innervation pattern across the endocrine as well as exocrine parts of the optically cleared tissues to examine if varying nerve supply to the islets could be a potential contributor to the disease. We found the three- dimensional models to provide distinctive information regarding the expression of Glial Fibrillary Acidic Protein (GFAP), an intermediate filament protein of the central nervous system, in human pancreas when compared with regular thin sections of paraffin embedded tissue.
Collectively, our results indicate that three- dimensional analysis of human pancreatic tissue could provide a more comprehensive, in- depth perspective of the human pancreatic tissue and thereby a highly potential methodology for understanding the pathogenesis of type 1 diabetes in human pancreatic tissues.