BDNF injected into the superior colliculus reduces developmental retinal ganglion cell death.
The role of neurotrophins as survival factors for developing CNS neurons, including retinal ganglion cells (RGCs), is uncertain. Null mutations for brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), individually or together, are without apparent effect on the number of RGCs that survive beyond the period of normal, developmental RGC death. This contrasts with the BDNF dependence of RGCs in vitro and the effectiveness of BDNF in reducing RGC loss after axotomy. To investigate the effect of target-derived neurotrophins on the survival of developing RGCs, we injected BDNF into the superior colliculus (SC) of neonatal hamsters. At the age when the rate of developmental RGC death is greatest, BDNF produces, 20 hr after injection, a 13-15-fold reduction in the rate of RGC pyknosis compared with the rates in vehicle-injected and untreated hamsters. There is no effect 8 hr after injection. Electrochemiluminescence immunoassay measurements of BDNF protein in the 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 pharmacological 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.
Ma
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Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Hsieh
T
T
Forbes
M E
ME
Johnson
J E
JE
Frost
D O
DO
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000493:pharmacokinetics / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D006224:Cricetinae; D005456:Fluorescent Dyes / Q000494:pharmacology; D007267:Injections; D008647:Mesocricetus; D012160:Retina / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology; D013477:Superior Colliculi / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
D000578:Amidines; D019208:Brain-Derived Neurotrophic Factor; D005456:Fluorescent Dyes; C037945:diamidino yellow