Role of Muller glial cells in the generation of neuroblasts and photoreceptor-like cells. Apoptosis prevention by sphingosine 1 phosphate

SIMON M.V.; DE GENARO P.; ABRAHAN CE; DE LOS SANTOS EB; ROTSTEIN N.P.; POLITI L.E.

Huerta Grande, Cordoba

Congreso; 1ª Reunión Conjunta SAN-Taller Argentino de Neurociencias; 2009

Sociedad Argentina de Investigacion en Neurociencias- Taller Argentino de Neurociencias

<!-- /* Font Definitions */ @font-face {font-family:Calibri; panose-1:2 15 5 2 2 2 4 3 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:-1610611985 1073750139 0 0 159 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin-top:0in; margin-right:0in; margin-bottom:10.0pt; margin-left:0in; mso-line-height-alt:8.0pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Calibri; mso-fareast-font-family:Calibri; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:ES-MX;} @page Section1 {size:8.5in 11.0in; margin:70.85pt 85.05pt 70.85pt 85.05pt; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Role of Muller glial cells in the generation of neuroblasts and photoreceptor-like cells.  Apoptosis prevention by sphingosine 1 phosphate  M.V. Simón;  P. de Genaro; C. Abrahan ; B. de los Santos; N. Rotstein  and L. Politi. Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), CONICET – Universidad Nacional del Sur, Bahía Blanca.   Apoptosis of photoreceptors (PR) is the main cause of blindness in retinal neurodegenerations. Since the finding of stem cells in the retina, a promising strategy to avoid vision impairment is to regenerate lost PR.  Using Muller glial cells (MGC), which display stem cell properties, requires establishing how MGC might generate neuroblasts (NB), how to induce these NB to further differentiate into mature neurons and how to avoid apoptosis of the regenerated neurons. To investigate these issues we used pure neuronal and glial primary and secondary cultures, and neuro-glia cocultures. NB, characterized as round, undifferentiated cells that took up Bromodeoxyuridine and expressed Nestin and Pax6, were only preserved in long-term primary and secondary neuro-glia cocultures, since they were absent or rapidly disappeared in pure neuronal or pure glial cultures. NB comprised about 63% of the total small, round cells in primary neuro-glia cocultures but dropped to 1% in secondary cocultures; concomitantly, nearly 70% and 10% of round cells in secondary cocultures expressed the PR markers Crx and opsin, respectively; these cells also showed high affinity glutamate uptake, a feature of functional PR. Apoptosis of PR-like cells increased during culture time but addition of sphingosine-1-phosphate (S1P), recently shown to prevent PR apoptosis, decreased their death. Our results suggest that neuron-MGC interactions might be relevant in the preservation or generation of NB and in their further differentiation as PR, while S1P might provide a useful tool to prevent apoptosis in newly generated PR.   Supported  by  Agencia Nacional de Promoción Científica;  CONICET y Universidad Nacional del Sur