Sphingosine-1-phosphate: life and death in the retina.

ROTSTEIN N.P.; SIMON M.V.; PRADO SPALM FH; VERA M; POLITI L.E.

San Pablo

Congreso; XXX Reunión Anual de la Federação de Sociedades de Biologia Experimental (FeSBE) de Brasil; 2015

Sphingosine-1-phosphate (S1P) is a potent sphingolipid mediator that regulates proliferation, survival, migration and inflammation in different cell types, acting on S1P membrane receptors (S1PRs) or as an intracellular messenger. S1P roles in the retina are still poorly understood. We have demonstrated that S1P promotes proliferation and differentiation in photoreceptors and rescues them from oxidative stress-induced apoptosis. We have now investigated the pathways leading to S1P protective effect. Our data evidence that S1P activates S1P3 and the ERK/MAPK pathway to protect photoreceptors from oxidative stress. As we showed that Müller glial cells rescues photoreceptors from oxidative stress-induced apoptosis, we explored whether S1P was involved in this protection. In neuro-glial cultures grown in S1P-lacking media, addition of an inhibitor of S1P synthesis or a S1PR antagonist blocks glial protection, suggesting glial cells synthesize and release S1P to promote photoreceptor survival.We also investigated whether S1P regulates the migration of Müller glial cells, known to be activated in proliferative retinopathies. We have found that glial cells synthesize S1P, which signals through S1P3 and the PI3K and ERK/MAPK pathways, activating metalloproteinases to induce glial migration. As a whole, our data point to a central role for S1P in the control of crucial processes in photoreceptors, glial cells and in neuron-glia crosstalk. Since deregulation of these processes is involved in several retinal pathologies, S1P signaling emerges as a potential tool for treating these diseases.