Exogenous application of gangliosides changes the state of excitability of retinal tissue as demonstrated by retinal spreading depression experiments

Abstract

Gangliosides are amphiphilic, sialic acid-containing glycosphingolipids which are found preferentially in complex composition in the cellular membranes of the nervous system of vertebrates, including the vertebrate retina as well as in other membranes. They are always exposed to the extracellular side of the membranes. By virtue of the negative charges they carry at their headgroup, they contribute to the surface charge of the membrane and may affect ion distribution, mainly that of protons and calcium ions, at the outer side of the membranes. Using retinal spreading depression (RSD) as a tool, we show in this study that the addition of exogenous gangliosides to the extracellular space can change the state of excitability of the retinal tissue. In RSD experiments it reduces the propagation velocity as well as the intrinsic optical signal of RSD waves. These effects are concentration dependent (IC₅₀ about 20 μM) and increase with the increasing negative charge of the ganglioside headgroup. As a possible mechanistic basis of the changes found, the change of the calcium homeostasis of the extracellular space by the exogenously added gangliosides is discussed. Gangliosides have been reported to be useful in the treatment of some neuropathological syndromes, including migraine, although experimental verification has not been possible up to now. Taking into account that the retina is a true part of the CNS, our data may be interpreted as the requested verification.