Department of Drug Design and Pharmacology > Employees
Dorte M. Skytt
Molecular and Cellular Pharmacology
Jagtvej 160, 2100 København Ø
The sight is a complex process in which the nerve signals transmitted over the retinal ganglion cells (RGC) through the optic nerve to the brain, where the image is finally formed. Thus, RGC are essential for the sight and treatment strategies for maintaining RGC will eventually be able to prevent blindness. One of the most common eye diseases, glaucoma, is characterized by a chronic progressive degeneration of the RGC. The cause of RGC death is not clear, but one of the recognized hypotheses explains cell death with the excitotoxic effects of the neurotransmitter glutamate. The glutamate-balance is maintained by the retinal support cells, Müller cells, but an imbalance in the retina may lead to oversignaling by glutamate. This leads to nerve cell death, which characterizes glaucoma. Studies from the brain have shown that the glutamate balance here is dependent upon intact energy input to the astrocytes; the glial support-cells in the brain. Similarly, one can imagine that the Müller cells' ability to remove glutamate from the synapse and thus maintain glutamate balance in the retina is dependent on a conserved energy supply. The Intracellular organelles, mitochondria, are an important component in cellular energy metabolism, and therefore it is obvious that the mitochondria are essential for homeostasis Müller cells - and hence their ability to protect the RGC is dependent on a highly conserved mitochondrial activity. In this project, we want just to illustrate the role of mitochondria in Müller cell homeostasis. To enlighten this we will: 1) Generate a transgenic mouse model with mitochondrial dysfunction specifically in Müller cells, 2) an in vitro model with co-cultures of Müller cells and RGC. Overall, our hypothesis is that mitochondrial activity is essential for the Müller cells' ability to maintain RGC. Thus, we imagine that treatment strategies aimed at Müller cell energy metabolism may eventually be relevant in the prevention and treatment of glaucoma.