AXOTOMY RESULTS IN DELAYED DEATH AND APOPTOSIS OF RETINAL GANGLION-CELLS IN ADULT-RATS

Using quantitative anatomical techniques, we show that after intraorbi tal optic nerve transection in adult rats, virtually all retinal gangl ion cells (RGCs) survive for 5 d and then die abruptly in large number s, reducing the RGC population to approximately 50% of normal by day T and to less than 10% on day 14. During this period of rapid cell loss , some RGCs show cytochemical alterations indicative of apoptosis (''p rogrammed cell death''), a change not previously categorized after axo tomy in adult mammals. With intracranial lesions 8-9 mm from the eye, the onset of cell death is delayed until day 8 and is greater with cut than crush. The demonstration that axotomy results in apoptosis, the long interval between axonal injury and RGC death, and the different t ime of onset of the massive RGC loss with optic nerve lesions near or far from the eye suggest that axonal interruption triggers a cascade o f molecular events whose outcome may be critically dependant on the av ailability of neuronal trophic support from endogenous or exogenous so urces. The role of such molecules in RGC survival and the reversible n ature of these injury-induced changes is underscored by the temporary rescue of most RGCs by a single intravitreal injection of brain-derive d neurotrophic factor during the first 5 d after intraorbital optic ne rve injury (Mansour-Robaey et al., 1994). The delayed pattern of RGC l oss observed in the present experiments likely explains such a critica l period for effective neurotrophin administration.