Apoptosis in adult retinal ganglion cells after axotomy

Abstract

Lesions to the mature mammalian central nervous system cause irreversible degeneration, in which neurons have been previously thought to be passive victims. In this study, axon-lesioned adult rat neurons are shown instead to actively degrade themselves through the process of apoptosis: a programmed type of cell death in which the cellular apparatus is actively involved in the degradation process. To investigate whether retinal ganglion cells of an adult mammal follow an apoptotic type of death when their axons are severed, DNA breaks in nuclei were labeled in situ, using a method that specifically incorporates biotinylated deoxynucleotides by exogenous terminal deoxynucleotidyl transferase on the 3'-OH ends of DNA. The active nature of the death mechanism was demonstrated by the reduction in biotin-labeled nuclei after administering the protein synthesis inhibitor cycloheximide. Our results suggest that retinal ganglion cells of the adult rat die through apoptosis when axotomized. This raises new possibilities in the treatment of CNS injuries, by the potential interruptibility of a program for neuronal death.

Reduction of Potassium Currents and Phosphatidylinositol 3-Kinase-Dependent Akt Phosphorylation by Tumor Necrosis Factor-α Rescues Axotomized Retinal Ganglion Cells from Retrograde Cell DeathIn Vivo

“…Transection of the ON induces a delayed death of 80 -90% of RGCs within 14 d, starting around day 4 and reaching a maximum on day 7 after axotomy (Eschweiler and Bähr, 1993;Mansour-Robaey et al, 1994). It has been shown that this retrograde cell death can be ascribed to apoptosis (Garcia-Valenzuela et al, 1994;Rabacchi et al, 1994;Isenmann et al, 1997). Caspase-3 (CPP32)-like protease has been identified as an important mediator of apoptotic RGC death in our experimental paradigm (Kermer et al, 1998(Kermer et al, , 1999b.…”

Lens Injury Stimulates Axon Regeneration in the Mature Rat Optic Nerve

“…In mature mammals, RGCs are unable to regrow injured axons and soon undergo apoptotic death (Garcia-Valenzuela et al, 1994). These well known events are a paradigm of regenerative failure in the CNS and may mimic pathophysiological sequelae that underlie degenerative diseases such as glaucoma (Quigley and Green, 1979;Quigley et al, 1995).…”

Animal models of optic nerve diseases

“…[42][43][44] One-half of them will degenerate 4 days after optic nerve axotomy, and it rises to about 70% in 1 week and to more than 95% in 2 weeks.…”