Sphingosine-1-phosphate has a key role in glial proliferation, migration and neuroprotection

ABRAHAN, C.E.; NAVALLAS, S.; POLITI, L.E.; ROTSTEIN, N.P.

Fort Lauderdale

Congreso; ARVO Annual Meeting; 2011

ARVO

Sphingosine-1-phosphate stimulates the proliferation and migration of Muller glial cells in vitro. Abrahan C.E., Navallas S.J., Politi L.E., Rotstein N.P. Instituto de Investigaciones Bioquímicas, Universidad Nacional del Sur (UNS)-CONICET. B. Blanca, Bs. As. Purpose:  Retinal damage induces proliferation and migration of Mueller glial cells, and these could lead dysfunctions of vision. Knowlegde of the mediators of these processes in Mueller cells could aid the development of therapeutical tools to control them. Sphingosine-1-phosphate (S1P) is a key sphingolipid on proliferation and migration of many cell types, and participates on vascular proliferation during retinal pathologies. The aims of this study was to determinate whether S1P regulates the proliferation and migration of Mueller cells in vitro, and whether this action on migration is mediated by activation of S1P3, a membrane receptor for S1P. Methods:  Rat Müller glial cells cultures were treated with or without 5µM S1P for 24 hours. The proliferation was evaluated by cell count  and bromodeoxiuridine (BrdU) or [3H]thimidine intake. The migration was studied on confluent Mueller cells treated with or without 5µM S1P for 8 hours by scratch-wound assay, or on retinal explants during 24 hours. The cytoskeleton organization was evaluated by phalloidin dye. To study whether the activation of S1P3 is necessary for S1P activity on migration, BML-241, an antagonist of it, was used. Results:  S1P lead to an increase on cell count, BrdU and [3H]thimidine intake on glial culture. Moreover, S1P promoted the glial migration on scratch-wound assay: S1P stimulated the number of cells that migrated from the scratch respect to the control, and same results were obtained in retinal explants.  The use of BML-241 blocked the migration stimulated by S1P in glial cells. Conclusions: S1P could participate as a potent stimulator of proliferation and migration on Mueller glial cells in vitro and the use of an antagonist of a S1P receptor could block the migration of them.