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Analysis of the neurovascular unit - implications for retinal vasoregression

Subject Area Ophthalmology
Endocrinology, Diabetology, Metabolism
Term from 2015 to 2019
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 269923409
 
In a number of diseases such as stroke, Morbus Alzheimer, and diabetic retinopathy, the interaction of blood vessels and neurons determines the level of organ failure and repair potential. As an example, in diabetic retinopathy, there is a large gap between the clinical diagnostics and treatment and the underlying pathogenesis: while retinopathy is clinically diagnosed and treated based only on vascular changes, the functional impairment which is of primary interest to the patient comes about from neuronal failure. The mutual influence of the individual components of the neurovascular unit in the development of vasoregression, however, is only poorly understood. We have examined the relationship between vasoregression and neurodegeneration in the retina of the PKD rat, and identified glial and microglial activation and upregulation of the innate immunity system as possible mediators of vasoregression. Therefore, we propose to modulate individual members of the neurovascular unit (neurons, vascular cells, glia, microglia) to understand their impact on vasoregression. Clodronate-coated liposomes will be used to abrogate microglia, inhibition of thesoluble epoxid hydrolase will be used to mitigate glial activation, and targeted replacement of pericytes cells will be accomplished by adipose-derived stem cells. In an attempt to develop the model into translational research, we propose to implement in vivo imaging and monitoring of neuronal function (optical coherence tomography, electroretinogram, fluorescence angiography and fundus imaging) using rodent adapted technologies.
DFG Programme Research Grants
 
 

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