Apoptosis Signaling In Retinas Of Mice With Inherited Photoreceptor Degeneration

The signaling pathways which lead to the wave of photoreceptor cell death in the rd mouse during the second week after birth have yet to be defined. The photoreceptors of these mice develop normally until they begin to elaborate phototransducing outer segments at around postnatal day (P)8. At this point, their differentiation slows as intracellular levels of cGMP rise due to the inherited mutation in the phosphodiesterase-β subunit.We have used an immunocytochemical approach to investigate potential signaling pathways leading to photoreceptor cell apoptosis in this mutant. The earliest change detected in the photoreceptor layer was an induction of CREB immunoreactivity in photoreceptor nuclei, commencing at P8. Although CREB is generally thought to be constitutively expressed and its function controlled primarily by its phosphorylation, we find that immature photoreceptors of normal mice are immunonegative for CREB until the time of eye opening and the initiation of phototransduction at around P14.