Ophthalmologisches Monitoring der diabetischen Neuropathie am Mausmodell

Zusammenfassung

Der Diabetes mellitus führt auch bei einer erfolgreichen Blutglukosekontrolle mit einer Normalisierung des HbA1c-Wertes bei Patienten häufig zu Spätkomplikationen, zu denen neben mikrovaskulären und makrovaskulären Schäden vor allem die diabetische Polyneuropathie zählt. Betroffen sind periphere Nerven, deren Schädigung zu Empfindungsstörungen und starken Schmerzen führen kann. Bei diesen Nerven handelt es sich vornehmlich um Aδ- und C-Fasern, die neben der Haut auch im subbasalen Nervenplexus der Kornea zu finden sind. Die Abbildung des subbasalen Nervenplexus mittels mikroskopischer Techniken ermöglicht eine sehr frühzeitige und objektive Darstellung der Neuropathie, wie sie mittels Hautbiopsie nur invasiv möglich ist. Wir haben einen thy1-YFP-Mausstamm verwendet, in dem periphere Nerven durch Fluoreszenzanregung darstellbar sind. Mittels 2-Photonen-Mikroskopie konnten wir hochauflösende 3-dimensionale Darstellungen des subbasalen Nervenplexus der Kornea dieser Mäuse generieren. Durch Injektion von Streptozotocin haben wir in thy1-YFP-Mäusen einen Diabetes mellitus induziert. Wir konnten zeigen, dass es parallel zum Anstieg der Blutglukose zu einem Verlust subbasaler Nervenfasern vor allem im Zentrum der Kornea kommt. Eine nachfolgende Behandlung der Tiere mit Insulin führte zur Normalisierung der Blutglukose und zu einer Zunahme der subbasalen Nervenfasern. Somit ist dieses Mausmodell sehr gut geeignet, die Pathogenese der diabetischen Polyneuropathie weiterführend zu untersuchen, mit dem Ziel, kausale Therapieansätze zu ihrer Behandlung zu entwickeln.

Abstract

Patients with diabetes mellitus suffer from late damage, including microvascular and macrovascular complications and diabetic polyneuropathy, even though blood glucose is well controlled and the HbA1c value normalised. Peripheral nerves are affected, and when these are damaged, this can result in disturbed sensation and pain. Such nerves are mainly Aδ und C fibres, which are present in the skin, but also in the subbasal nerve plexus of the cornea. Imaging of the subbasal nerve plexus using microscopic techniques allows a very early and objective view of neuropathy, which is only possible invasively by skin biopsy. We have used a thy1-YFP mouse strain in which the peripheral nerves are detectable by fluorescence excitation. Using two photon microscopy, we produced high resolution three dimensional images of the corneal subbasal nerve plexus of these mice. We induced diabetes mellitus in thy1-YFP mice by injection of streptocotocin. We showed that the increase in blood glucose was accompanied by a loss of subbasal nerve fibres, mainly in the centre of the cornea. Subsequent treatment of the animals with insulin normalised blood glucose and was accompanied by an increase in subbasal nerve fibres. Thus, this model is highly suited to investigate the pathogenesis of diabetic polyneuropathy, with the aim of developing new causal strategies to treat the disease.

Schlüsselwörter

diabetische Neuropathie - periphere Nervenfasern - Kornea - 2-Photonen-Mikroskopie - thy1-YFP-Maus

Key words

diabetic neuropathy - peripheral nerve fibres - cornea - two-photon microscopy - thy1-YFP mouse

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