Functions of retinoic acid during photoreceptor development in vitro

DE GENARO, P.; SIMÓN, V.; ROTSTEIN, N.P.; POLITI, L.E.

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2011

Functions of Retinoic Acid during photoreceptor development in vitro.   De Genaro P, Simón V, Rotstein N, Politi L. Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) and Universidad Nacional del Sur (UNS). Bahía Blanca, Argentina. E-mail: pdgenaro@criba.edu.ar   Retinoic acid (RA) has a critical role in promoting cell differentiation in several tissues, including the retina. In addition, RA induces apoptosis in diverse cell types. In this work we investigated the effects of RA in retina rod photoreceptors (PHRs). Cultures prepared from newborn rat retinas, grown in chemically defined media, were supplemented with RA and/or docosahexaenoic acid (DHA), a molecule that promotes PHR survival. RA advanced PHR differentiation: it increased opsin and peripherin expression and promoted axon outgrowth in PHRs. Activation of p38 was involved in RA effects. RA promoted the phosphorylation of p38, while a p38 inhibitor blocked RA effect on PHR differentiation. RA also accelerated the onset of PHR apoptosis, which occurs in cultures lacking PHR trophic factors. RA-induced apoptosis was blocked with a caspase inhibitor and also prevented by pre-incubating the cultures with DHA.  In summary, this work shows that RA induced both the early differentiation and apoptosis of PHRs in vitro and this death can be prevented by DHA. These results suggest that since RA is critical to stimulate PHR early differentiation, PHRs require a simultaneous provision of survival factors to advance their differentiation and avoid cell death during development.