INIBIBB   05455
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BAHIA BLANCA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Sphingosine-1-phosphate promotes the proliferation and differentiation of retina photoreceptors.
Autor/es:
MIRANDA G.E.; ROTSTEIN N.P.
Lugar:
Búzios, Rio de Janeiro, Brasil
Reunión:
Congreso; I Congresso IBRO/LARC de Neurosciencias da America Latina Caribe e Península Ibérica (Neurolatam); 2008
Institución organizadora:
Neurolatam, IBRO-LARC
Resumen:
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SPHINGOSINE-1-PHOSPHATE
PROMOTES THE PROLIFERATION AND DIFFERENTIATION OF RETINA PHOTORECEPTORS
Gisela E. Miranda and Nora
P. Rotstein.
Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad
Nacional del Sur (UNS), Bahía Blanca, Buenos Aires, Argentina.
Objective: docosahexaenoic acid (DHA), the
major polyunsaturated fatty acid in the retina, prevents apoptosis and promotes
differentiation of photoreceptors. DHA decreases the levels of ceramide to
promote photoreceptor survival (IOVS 47:1658, 2006) suggesting that sphingolipids
might mediate other effects of DHA on photoreceptors. We now investigated
whether sphingosine-1-phophate (S1P) regulates proliferation and
differentiation in photoreceptors.
Methods: Pure rat retina neurons in culture
were supplemented with or without DHA or GDNF and/or S1P. The cultures were
also treated with an inhibitor of Sphingosine Kinase (SK) to block S1P
synthesis, or with Brefeldin A (BFA) which collapses the Golgi into the ER. Photoreceptor
differentiation was determined by evaluating the amount of apical processes and
opsin and peripherin expression. Proliferation was evaluated counting mitotic
figures and BrdU uptake.
Results: photoreceptors in control
cultures had few apical processes and opsin was distributed over the whole cell
body and neurites. S1P or DHA enhanced the development of apical processes,
increased opsin and peripherin expression and promoted their localization in
apical processes. Inhibiting S1P synthesis blocked DHA-induced increase in
photoreceptor differentiation and addition of S1P to these cultures restored
photoreceptor differentiation. Treatment of DHA or S1P-supplemented cultures
with Brefeldin A decreased the formation of apical processes, without affecting
opsin or peripherin expression. Though S1P and DHA had similar effects on
differentiation, they did not share their effect on proliferation. DHA induces
the exit of photoreceptor progenitors from the cell cycle while glial derived
neurotrophic factor (GDNF) promotes their proliferation. S1P treatment enhanced
proliferation of photoreceptor progenitors, while inhibition of S1P synthesis
blocked GDNF effect on proliferation.
Conclusions: These results suggest that S1P is a key mediator
in photoreceptor proliferation and differentiation; GDNF and DHA might enhance
its synthesis at different times in development to regulate the former the amount
of photoreceptors and the latter their differentiation.