APOPTOSIS IN ADULT RETINAL GANGLION-CELLS AFTER AXOTOMY

Lesions to the mature mammalian central nervous system cause irreversi ble degeneration, in which neurons have been previously thought to be passive victims. In this study, axon-lesioned adult rat neurons are sh own instead to actively degrade themselves through the process of apop tosis: a programmed type of cell death in which the cellular apparatus is actively involved in the degradation process. To investigate wheth er retinal ganglion cells of an adult mammal follow an apoptotic type of death when their axons are severed, DNA breaks in nuclei were label ed in situ, using a method that specifically incorporates biotinylated deoxynucleotides by exogenous terminal deoxynucleotidyl transferase o n the 3'-OH ends of DNA. The active nature of the death mechanism was demonstrated by the reduction in biotin-labeled nuclei after administe ring the protein synthesis inhibitor cycloheximide. Our results sugges t that retinal ganglion cells of the adult rat die through apoptosis w hen axotomized. This raises new possibilities in the treatment of CNS injuries, by the potential interruptibility of a program for neuronal death. (C) 1994 John Wiley and Sons, Inc.