Docosahexaenoic acid (DHA) and sphingosine-1-phosphate (S1P) promote survival and spatial reorganization of photoreceptor neurons generated in vitro by Müller glia stem cells.

DIBO M; SIMON M.V.; GERMAN O.L.; VOLONTÉ Y.; ROTSTEIN N.P.; POLITI L.E.

Puerto Iguazú, Misiones

Congreso; 56th International Conference on the Bioscience of Lipids (ICBL); 2015

ICBL

DOCOSAHEXAENOIC ACID (DHA) AND SPHINGOSINE-1-PHOSPHATE (S1P) PROMOTE SURVIVAL OF PHOTORECEPTOR NEURONS AND ACQUISITION OF NEURONAL PROPERTIES BY MÜLLER GLIA STEM CELLS IN VITRO Simón MV, Dibo, M, Volonté Y, German L, Rotstein NP and Politi LE. Instituto de Investigaciones Bioquímicas, Universidad Nacional del Sur-CONICET, Bahía Blanca.E-mail: inpoliti@criba.edu.arRegeneration of neurons using stem cells would help to provide a suitable treatment for retina neurodegenerations as Retinitis Pigmentosa or Macular Degeneration, two diseases in which photoreceptor neurons (PHR) degenerate by apoptosis leading to blindness. It has been reported that Müller glial cells (MGC) are stem cells, potentially able to regenerate the retina. Unfortunately, in those animal models in which neurons were regenerated, these new cells ended up developing apoptosis. We have previously established that DHA and S1P promote PHR survival, and that MGC in secondary cultures transform retinal progenitors in multipotent stem cells, which differentiate into PHR. We here investigated whether DHA and S1P can improve survival of PHR generated by MGC. Secondary neuro-glial cultures were incubated with neuronal differentiation media supplemented with either, vehicle (control) or with 6.7 µM or 1 µM S1P for 6 days and then fixed and analyzed by different cytochemical methods to evaluate apoptosis, and the occurrence of PHR or amacrine neuronal markers. DHA and S1P significantly reduced PHR apoptosis compared to controls. Noteworthy, DHA promoted the expression of the transcription factor Crx, an early marker of PHR differentiation in MGC.These results suggest that S1P and DHA interact with MGC controlling the differentiation pathway of PHR generated from stem cells in vitro and enhancing their further survival.