Endocrine Abstracts

Introduction: Major advances in the research and treatment of diabetes-related neuropathic phenomena are hampered due to its complicated pathophysiology and the scarcity of valid experimental models. The aim of this study was to establish novel systems facilitating monitoring and dissection of processes central to the development of diabetic neuropathy.

Methods: In a non-invasive in vivo model, two-photon microscopy is used to detect and assess mechanoreceptors (Meissner’s corpuscles) in whole footpads of mice carrying a neuronal genetic tracer. This technology offers a potent tissue penetration capacity coupled by superb resolution. The illustrated ex vivo system simulates the native microenvironment of the nerve ending by a unique co-culture of primary sensory neurons and freshly harvested skin from control or diabetic mice. Innovative high-throughput tools were used to quantify the growth of hundreds of neurons in a non-biased manner.

Results: Qualitative and quantitative alterations in Meissner’s corpuscles in an intact footpad of diabetic animals were detected in vivo, the results corroborated with parallel histopathological studies comparing control and diabetic animals. The ex vivo assays demonstrated that neurons from either control or diabetic mice have similar basal growth and that both show substantial growth enhancement upon exposure to skin-derived cues. However, the ability of diabetic skin to support such growth was dramatically diminished.

Conclusions: A non-invasive imaging of genetically traced Meissner’s corpuscles by two-photon microscopy offers a robust model to assess diabetes-induced distal axonal degeneration. The degeneration was found to correlate with target-organ malfunction rather than intrinsic neuronal factors. Moreover, diabetic neurons preserve their tentative ability to respond to skin-derived cues, thus may fully regenerate.