Brain Advance Access published online on January 17, 2006
Brain, doi:10.1093/brain/awl015
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1 Department of Pathology and Cell Biology, Université de Montréal, Quebec, Canada
* To whom correspondence should be addressed. Trauma or disease in the CNS often leads to neuronal death and consequent loss of functional connections. The idea has been put forward that strategies aimed at repairing the injured CNS involve stimulation of both neuronal survival and axon regeneration. We tested this hypothesis in the adult rat retinocollicular system by combining two strategies: (i) exogenous administration of brain-derived neurotrophic factor (BDNF), a potent survival factor for damaged retinal ganglion cells (RGCs) and (ii) lens injury, which promotes robust growth of transected RGC axons. Our results demonstrate that BDNF and lens injury interact synergistically to promote neuronal survival: 71% of RGCs were alive at 2 weeks after optic nerve injury, a time when only
Received July 12, 2005
Revised December 14, 2005
Accepted December 22, 2005
Article
Synergistic action of brain-derived neurotrophic factor and lens injury promotes retinal ganglion cell survival, but leads to optic nerve dystrophy in vivo
Vincent Pernet 1
and
Adriana Di Polo 2 *
2 Department of Pathology and Cell Biology, Université de Montréal, Quebec, Canada; Department of Ophthalmology, Université de Montréal, Quebec, Canada
Adriana Di Polo, E-mail: adriana.di.polo{at}umontreal.ca
Abstract 
10% of these neurons remain without treatment. Intravitreal injection of BDNF, however, led to regeneration failure following lens injury. The effect of BDNF could not be generalized to other growth factors, as ciliary neurotrophic factor did not cause a significant reduction of lens injury-induced regeneration. Growth arrest in optic nerves treated with BDNF and lens injury correlated with the formation of hypertrophic axonal swellings in the proximal optic nerve. These swellings were filled with numerous vesicular bodies, disorganized neurofilaments and degenerating organelles. Our results demonstrate that: (i) increased neuronal survival does not necessarily lead to enhanced axon regeneration and (ii) activation of survival and growth pathways may produce axonal dystrophy similar to that found in neurodegenerative disorders including glaucoma, Alzheimer's disease and multiple sclerosis. We propose that loss of axonal integrity may limit neuronal recovery in the injured, adult CNS.
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