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The Journal of Neuroscience, May 1, 1998, 18(9):3351-3362
Brain-Derived Neurotrophic Factor Modulates the Development of
the Dopaminergic Network in the Rodent Retina
Alessandro
Cellerino1,
Germán
Pinzón-Duarte1,
Patrick
Carroll2, and
Konrad
Kohler1
1 Division of Experimental Ophthalmology, Department of
Neuroophthalmology, University Eye Hospital, D-72076 Tübingen,
Germany, and 2 Institut National de la Santé et de la
Recherche Médicale Unit 382, IBDM, Luminy, 13288 Marseilles 09, France
Dopaminergic cells in the retina express the receptor for
brain-derived neurotrophic factor (BDNF) ().
To investigate whether BDNF can influence the development of the
retinal dopaminergic pathway, we performed intraocular injections of
BDNF during the second or third postnatal week and visualized the
dopaminergic system with tyrosine hydroxylase (TH) immunohistochemistry. Both regimens of BDNF treatment caused an increase in TH immunoreactivity in stratum 1 and stratum 3 of the inner
plexiform layer (IPL). D2 dopamine receptor immunoreactivity, a
presynaptic marker of dopaminergic cells (), was also
increased in stratum 1 and stratum 3 of the inner plexiform layer.
These data suggest that BDNF causes sprouting of dopaminergic fibers in
the inner plexiform layer. Other neurochemical systems, for example,
the cholinergic amacrine cells, remained unaffected. Similar effects
were observed after injections of neurotrophin-3 and neurotrophin-4,
but not nerve growth factor. Analysis of whole-mounted TH-immunolabeled
retinae revealed hypertrophy of dopaminergic cells (+41% in soma
areas; p < 0.01) and an increase of
labeled dopaminergic varicosities in stratum 1 of the IPL (+51%;
p < 0.01) after BDNF treatment. The opposite was
observed in mice homozygous for a null mutation of the
bdnf gene: dopaminergic cells were atrophic ( 22.5% in
soma areas; p < 0.05), and the density of TH-positive varicosities in stratum 1 was reduced (57%;
p < 0.01). We conclude that BDNF controls the
development of the retinal dopaminergic network and may be particularly
important in determining the density of dopaminergic innervation in the
retina.
Key words:
neurotrophin; growth factor; retina; inner plexiform
layer; amacrine neuron; development; synaptogenesis; BDNF knock-out
mouse; Parkinson's disease
Copyright © 1998 Society for Neuroscience 0270-6474/98/1893351-12$05.00/0
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