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Carolina E. Abrahan, Santiago J. Navallas, Luis E. Politi, Nora P. Rotstein; Sphingosine-1-Phosphate Has A Key Role In Müller Glia Proliferation, Migration And Neuroprotection. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2681.
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Sphingolipids are a group of lipids with key functions on cell proliferation, migration and survival and are emerging as possible tools for controlling these processes. We have identified the sphingolipid sphingosine-1-phosphate (S1P) as a crucial mediator in photoreceptor proliferation and survival. We have also shown that Müller glial cells in co-culture with retinal neurons protect neurons from oxidative stress, which in turn enhances glial proliferation. In this study we investigated the roles of S1P in proliferation and migration of Müller cells and in glial neuroprotection in vitro.
Pure glial cultures, retinal explants and neuroglial co-cultures were prepared from rat retinas. The effect of S1P on glial proliferation was evaluated by Br-deoxyuridine (BrdU) and [3H]thymidine uptake. Glial migration was studied by scratch-wound assays using confluent Müller cells or on retinal explants treated with or without S1P. To evaluate whether the activation of a S1P receptor (S1P3) was necessary for S1P activity we added BML-241, a S1P3 antagonist. S1P involvement in neuroprotection was investigated by treating co-cultures with BML-241 or with an inhibitor of S1P synthesis, and oxidative stress was then induced with the oxidant paraquat (PQ). Apoptosis was evaluated by TUNEL labeling.
Addition of S1P promoted [3H]thymidine and BrdU uptake and increased the number of cells in pure glial cultures. S1P also stimulated glial migration on scratch-wound assays, and this migration was blocked by BML-241 addition. Inhibiting S1P synthesis or adding BML-241 before treating neuroglial co-cultures with PQ blocked glial protection of retinal neurons from oxidative stress-induced apoptosis.
These results suggest that S1P might act as a potent stimulator of proliferation and migration of Müller glial cells in vitro. S1P might also be one of the key mediators released by glial cells to prevent neuronal apoptosis.
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