(-)-DEPRENYL INCREASES THE SURVIVAL OF RAT RETINAL GANGLION-CELLS AFTER OPTIC-NERVE CRUSH

Retinal ganglion cells (RGCs) have been shown to die by apoptosis after damage to their axons caused by optic nerve crush and the death can be reduced by some neurotrophic factors. Since (-)-deprenyl can reduce apoptotic death in some neuronal systems, we determined whether it can increase RGC survival after optic nerve crush. Fluoro-Gold (FG), a fluorescent retrograde tracer, was injected into both superior colliculi to pre-label RGC cells bodies in the retinal ganglion cell layers (RGCLs) of adult Sprague-Dawley rats. Fours days later, the left optic nerve was crushed immediately behind the globe and the animals received either (-)-deprenyl (1 mg/kg) or saline by intraperitoneal injection every two days for 14 days. Nissl stained neuronal cell bodies per mm of section length of RGCL were counted from serial frozen sections. The number of RGCL cell bodies sending axons to the superior colliculi (RGC(SC)s) were identified by FG fluorescence as a means of determining the proportion of RGCL neurons (RGCLns) that were RGC(SC)s. In the uncrushed retinas an average of 40.7% of the RGCLns were found to be RGC(SC)s. There was no difference in RGC(SC)s /mm between the uncrushed treated with saline group and the uncrushed group treated with (-)-deprenyl group. The optic nerve crush with saline group showed a decrease in RGC(SC)s to 3.0 +/- 1.0% of the uncrushed saline group while the optic nerve crush with (-)-deprenyl group showed a considerably smaller decrease in RGC(SC)s to 36.9 +/- 11.2% of the uncrushed saline group. The results show that (-)-deprenyl increases the survival of rat RGCs at 14 days after optic nerve crush, possibly through a transcriptionally-dependent blockade of apoptosis similar to that previously found for (-)-deprenyl in vitro.