From: Retinoic Acid Promotes Apoptosis and Differentiation in Photoreceptors by Activating the P38 MAP Kinase Pathway Invest. Ophthalmol. Vis. Sci.. 2013;54(5):3143-3156. doi:10.1167/iovs.12-11049 Figure Legend: Mechanisms of RA effects on retina photoreceptors. During early stages of retina development (left panel), when retina progenitors still were progressing in the cell cycle, RA bound and activated its nuclear receptors (RAR and RXR) to activate the p38 MAPK signaling pathway. Activation of this pathway was crucial for induction of apoptosis and also involved in promoting photoreceptor differentiation, together with other signaling cascades, which are likely to be triggered by RAR/RXR activation. DHA, a photoreceptor trophic factor, prevented cell death probably by activating the ERK/MAPK pathway, 38 which blocked the apoptotic signal downstream of p38 activation. In post mitotic photoreceptors (right panel) RA lost its capacity to activate the p38 pathway and no longer induced apoptosis; however, it still promoted differentiation, most likely by acting through other, still undefined, signaling pathways. Date of download: 10/7/2017 The Association for Research in Vision and Ophthalmology Copyright © 2017. All rights reserved.