INIBIBB   05455
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BAHIA BLANCA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Sphingosine-1-phosphate: a key mediator in the development of retina photoreceptors.
Autor/es:
MIRANDA G.E.; ROTSTEIN N.P.
Lugar:
Bahia Blanca, Buenos Aires
Reunión:
Workshop; Workshop: Neuronal Communication: From Structure to Physiology.; 2008
Institución organizadora:
Sociedad Argentina de Investigacion en Neurociencias
Resumen:
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SPHINGOSINE-1-PHOSPHATE:
A KEY MEDIATOR IN THE DEVELOPMENT 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.
Docosahexaenoic
acid (DHA), the major polyunsaturated fatty acid in the retina, and Glial
Derived Neurotrofic Factor (GDNF) promote survival and differentiation, and
proliferation of photoreceptors, respectively. 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), a sphingolipid known to promote survival
and proliferation in several cell types, regulates proliferation and
differentiation in rat retina photoreceptors in culture.
Supplementation
with DHA or S1P enhanced the development of apical processes, increased opsin
and peripherin expression and promoted their localization in these processes. While
inhibition of S1P synthesis, using an inhibitor of Sphingosine Kinase (SK), blocked
DHA-induced increase in photoreceptor differentiation, addition of S1P to these
cultures restored photoreceptor differentiation. Treatment of DHA or
S1P-supplemented cultures with Brefeldin A, which collapses the Golgi into the
ER, decreased the formation of apical processes, without affecting opsin or
peripherin expression.
We have
previously shown that GDNF promoted the proliferation of photoreceptor
progenitors. S1P also enhanced this proliferation and, interestingly,
inhibition of its synthesis blocked GDNF effect on proliferation. When the
effect of DHA and GDNF on SK expression was investigated, both trophic factors
were found to increase the levels of SK in photoreceptors.
These data suggest that at different times during
development GDNF and DHA might enhance S1P synthesis through an increase in SK
levels, to regulate the amount of photoreceptors and their differentiation, respectively.
Conversely, inhibiting S1P synthesis blocks both processes. Hence, our results
support the proposal of S1P as a key mediator in photoreceptor proliferation
and differentiation.