Kurzfassung

The photoreceptors (rods and cones) are cell types exhibiting the greatest energy demand in the organism. As a by-product of energy generation they form reactive oxygen species (ROS), and in particular superoxide (O2-), and in this way induces oxidative stress in their environment. The regulation of photoreceptor energy metabolism is of major clinical relevance. Thus, dysregulation of photoreceptor energy metabolism results in increased superoxide formation contributes to the pathogenesis of...The photoreceptors (rods and cones) are cell types exhibiting the greatest energy demand in the organism. As a by-product of energy generation they form reactive oxygen species (ROS), and in particular superoxide (O2-), and in this way induces oxidative stress in their environment. The regulation of photoreceptor energy metabolism is of major clinical relevance. Thus, dysregulation of photoreceptor energy metabolism results in increased superoxide formation contributes to the pathogenesis of diabetic retinopathy - one of the most common causes of blindness in Europe and the USA. The metabolic rate and superoxide formation of photoreceptor cells display daily rhythms, with higher values at night. Preparatory work carried out for the proposed project demonstrates - through the example of the enzymes of fatty acid oxidation - that this is due to the clock-dependent regulation of the expression of metabolic key enzymes. The aim of the proposed project is to analyze circadian regulation of photoreceptor energy metabolism with regard to the involvement of relevant key enzymes, neuromodulators (melatonin and dopamine) and transcription factors. Furthermore, it should be investigated as to how far “circadian dysregulation” of energy metabolism and superoxide formation contributes to the pathogenesis of diabetic retinopathy. The proposed project can be considered as basic research that investigates circadian control of energy metabolism in a clinical context.
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