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A more recent version of this article appeared on March 1, 2009
(Investigative Ophthalmology and Visual Science. )
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2244

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Article

Exogenous brain-derived neurotrophic factor (BDNF) reverts phenotypic changes in the retina of transgenic mice lacking the bdnf gene

Blanca Arango-Gonzalez 1*, Alessandro Cellerino 2, and Konrad Kohler 3

1 Institute for Ophthalmic Research, Division of Experimental Ophthalmology, Centre for Ophthalmologie, Roentgenweg 11, Tuebingen, D-72076, Germany
2 Scuola Normale Superiore and Istituto di Neurofisiologia, Consiglio Nazionale delle Ricerche, Pisa, Italy
3 Division of Experimental Ophthalmology, Centre for Ophthalmologie, Institute for Ophthalmic Research, Tuebingen, Germany

* To whom correspondence should be addressed. E-mail: blanca.arango-gonzalez{at}klinikum.uni-tuebingen.de.


   Abstract

Purpose: We have investigated the effect of brain derived neurotrophic factor (BDNF) administration on the expression of Ca2+-binding proteins in the developing bdnf-/- mouse retina. Methods: An intraocular injection of BDNF (0.5 µg) was applied on postnatal day (PN) 11 bdnf-/- mice and its effect evaluated on PN14. Neurons expressing Ca2+-binding protein were studied by immunohistochemistry for protein kinase C {alpha}, recoverin, calbindin-D28K, calretinin and parvalbumin. Results: Cell density and immunostaining intensity for Ca2+-binding proteins in horizontal, bipolar, amacrine and ganglion cells were lower in the retinas of bdnf-/- mice than in those of the wild type (wt). Mutant retinas treated with BDNF showed a 35-40 % increase in the number of calbindin-positive horizontal and amacrine cells. An increase of 30 and 50 %, respectively, was also observed for calretinin- and parvalbumin-positive cells in the INL after BDNF treatment. The retinas of bdnf-/- mice showed expression of recoverin only in scattered bipolar cells; however, recoverin-positive bipolar cells were readily detectable after BDNF injection in mutants (80% increase). The number of parvalbumin-positive ganglion cells after BDNF treatment reached 100 % of control values. Expression of calretinin and calbindin was also up-regulated in the GCL of BDNF-treated mutants. Conclusions: The expression of Ca2+-binding proteins is reduced in the mutant retina. This neurochemical phenotype can be reverted, at least partially, by providing exogenous BDNF during the second week of postnatal development

Key Words: development, ocular, intravitreal drug delivery, amacrine cell, bipolar cell, ganglion cell, horizontal cell







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