Glaucomatous optic neuropathies (GONs), a major cause of blindness in developed countries, are characterized by progressive degeneration of retinal ganglion cells and their axons, leading to visual pathway deactivation. The degenerative as well as plasticity mechanisms at the level of respectively retina/optic nerve and visual cortex, are tightly intermingled with proper/dysfunctional glutamate (glu) neurotransmission as well as oxidative stress-related processes. Indeed, glu, the most important excitatory neurotransmitter in the central nervous system (CNS), drives processes of brain plasticity but can at the same time induce cell death when present at high extracellular levels. Also a deficit in intracellular glutathione (GSH) levels, the major antioxidant in CNS, can induce cell death and interfere with proper glu-ergic transmission. In this respect, system Xc- is an interesting target to investigate in GONs. At the level of the retina, optic nerve as well as visual cortex, malfunctioning or overactivation of this antiporter can have major dual implications, as this antiporter imports a cystine molecule in exchange for glu, thereby affecting intracellular GSH production as well as extracellular glu levels. Increased activity can thus protect cells by increasing antioxidant capacity, but at the same time kill cells by inducing glu toxicity. Within this project we will unravel the role of system Xc- in GONs using several complementary approaches and cutting-edge technologies.
|Effective start/end date||1/01/13 → 31/12/16|
- system xc-
- visual system
Flemish discipline codes