EXOGENOUS APPLICATION OF GANGLIOSIDES CHANGES THE STATE OF EXCITABILITY OF RETINAL TISSUE AS DEMONSTRATED BY RETINAL SPREADING DEPRESSION EXPERIMENTS

Gangliosides are amphiphilic, sialic acid-containing glycosphingolipid s which are found preferentially in complex composition in the cellula r membranes of the nervous system of vertebrates, including the verteb rate retina as well as in other membranes. They are always exposed to the extracellular side of the membranes. By virtue of the negative cha rges they carry at their headgroup, they contribute to the surface cha rge of the membrane and may affect ion distribution, mainly that of pr otons and calcium ions, at the outer side of the membranes. Using reti nal spreading depression (RSD) as a tool, we show in this study that t he addition of exogenous gangliosides to the extracellular space can c hange the state of excitability of the retinal tissue. In RSD experime nts it reduces the propagation velocity as well as the intrinsic optic al signal of RSD waves. These effects are concentration dependent (IC5 0 about 20 mu M) and increase with the increasing negative charge of t he ganglioside headgroup. As a possible mechanistic basis of the chang es found, the change of the calcium homeostasis of the extracellular s pace by the exogenously added gangliosides is discussed. Gangliosides have been reported to be useful in the treatment of some neuropatholog ical 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 requeste d verification.