BDNF INJECTED INTO THE SUPERIOR COLLICULUS REDUCES DEVELOPMENTAL RETINAL GANGLION-CELL DEATH

The role of neurotrophins as survival factors for developing CNS neuro ns, including retinal ganglion cells (RGCs), is uncertain. Null mutati ons for brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT 4), individually or together, are without apparent effect on the numbe r of RGCs that survive beyond the period of normal, developmental RGC death. This contrasts with the BDNF dependence of RGCs in vitro and th e effectiveness of BDNF in reducing RGC loss after axotomy. To investi gate the effect of target-derived neurotrophins on the survival of dev eloping RGCs, we injected BDNF into the superior colliculus (SC) of ne onatal hamsters. At the age when the rate of developmental RGC death i s greatest, BDNF produces, 20 hr after injection, a 13-15-fold reducti on in the rate of RGC pyknosis compared with the rates in vehicle-inje cted and untreated hamsters. There is no effect 8 hr after injection. Electrochemiluminescence immunoassay measurements of BDNF protein in t he retinae and SC of normal and BDNF-treated hamsters demonstrate that the time course of BDNF transport to RGCs supports a role for target- derived BDNF in promoting RGC survival. The effectiveness of pharmacol ogical doses of BDNF in reducing developmental RGC death may be useful in further studies of the mechanisms of stabilization and elimination of immature central neurons.