Retinoic Acid stimulates the differentiation of retina photoreceptors in vitro

DE GENARO, P; ROTSTEIN, NP; POLITI, LE

Montevideo

Simposio; International Symposium: Development and Plasticity of the Nervous System; 2010

Retinoic Acid (RA), a vitamin A prime metabolite, is crucial for correct eye development and photoreceptor (PR) differentiation. We here investigated its effects on early PR development and the intracellular pathways involved. Pure neuronal cultures obtained from 2 day old rat retinae were suplemented with or without 10 nM RA a few hours after plating. RA almost doubled the amount of cells expressing opsin and stimulated the expression of peripherin, a disc structural component, and the formation of apical processes in PRs at every time studied. We then assessed the activation of p38-MAPK, which is involved in RA receptor phosphorylation; RA readily increased phosphorylated p38 levels whereas total p38 remained unchanged. Addition of SB203580, a p38 inhibitor, led to a partial reversion of RA-stimulated opsin expression. We next studied the participation of PI3K, which is thought to have opposite effects to those of p38. Opsin expression was higher in cultures treated with RA plus Wortmannin or LY294002, PI3K inhibitors, than in those only with RA, suggesting RA might negatively regulate PI3K. In summary this work shows that RA promotes early development in vitro of PRs and this stimulation may occur, at least in part, through p38-MAPK activation and negative regulation of PI3K.