Diabetic retinopathy as a disease of the neurovascular unit – the role of inflammation and immune cell activation
Fördersumme: 22.000 €
To establish in vivo tracking of microglia cells and differentiate between residential and recruted microglia. To assess how inflammatory activation triggers neurovascular degeneration in the diabetic retina, and to dissect the relate contribution of endothelial, mural, glia, neural and immune cell components, we will use specific mouse models allowing to track immune cells in vivo.
The eye as a window to body vasculature: Leveraging dynamic retinal vessel analysis to understand vascular diseasis
Fördersumme: 142.297 €
The project investigates the hypothesis of dynamic retinal vessel analysis being the more sensitive method in detecting early vascular changes in the STZ (streptozocin) model of diabetic retinpathy. STZ induces diabetes is the most abundant model of Type I diabetes which enables visualization of initial diabetes induced vascular changes as early as two weeks after initiation of diabetes (vascular leakage).
After a technical validation phase of the method, a longitudinal study in rats treated with STZ will be performed. Dynamic and conventional vessel analysis will be conducted before STZ treatment and at three timepoints thereafter. Signature features of diabetic retinopathy will present at various time points during the course of the follow-up, with leakage of vessels being the primary alteration visible as early as two weeks after induction of diabetes. Leukostasis is detectable at four weeks, histological changes (capillary dropout, pericyte loss) after more than 6 months of diabetes.
The team behind this project proposal is part of a preparation effort for a collaborative research grant application at DFG (DFG Forschergruppe). This potential future project aims at investigating alterations of ocular vasculature in the context of various systemic vascular diseases. Dynamic vessel analysis in rodent models and humans will be an important part. Besides a pateient study, also diabetes/diabetic retinopathy models beyond the STZ model will be part of this follow-on project. Hence the here proposed project is embedded into a broader context and a sustainable interdisciplinary research agenda at Charité.