Apoptosis in the developing retina: paradoxical effects of protein synthesis inhibition

Cell death by apoptosis is usually characterized as an active process that requires protein and RNA synthesis. The requirement of protein synthesis for the degeneration of ganglion cells and other cell types was studied in neural retinae explanted from the eyes of newborn rats. Ganglion cells were detected by the presence of retrogradely transported horseradish peroxidase injected into the superior colliculus. Apoptotic cells were recognized by their condensed and deeply stained chromatin. The data show that the death of ganglion cells, whose axons are damaged when preparing the explants, is blocked or delayed by protein synthesis inhibitors. In contrast, the blockade of protein synthesis produced cell death with apoptotic morphology in the neuroblastic layer of the same retinae. The results suggest the operation in the developing retina of both a program of apoptosis dependent on the synthesis of killer proteins, and a latent mechanism of apoptosis that is normally blocked by repressor proteins.