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Blanca Arango-González, Alessandro Cellerino, Konrad Kohler; Exogenous Brain-Derived Neurotrophic Factor (BDNF) Reverts Phenotypic Changes in the Retinas of Transgenic Mice Lacking the bdnf Gene. Invest. Ophthalmol. Vis. Sci. 2009;50(3):1416-1422. doi: 10.1167/iovs.08-2244.
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purpose. The authors investigated the effect of brain-derived neurotrophic factor (BDNF) administration on the expression of Ca2+-binding proteins in the developing bdnf −/− mouse retina.
methods. Intraocular injections of BDNF (0.5 μg) were applied on postnatal day (P) 11 bdnf −/− mice, and their effects were evaluated on P14. Neurons expressing Ca2+-binding protein were studied by immunohistochemistry for PKC-α, 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 of wild-type mice. Mutant retinas treated with BDNF showed a 35% to 40% increase in the number of calbindin-positive horizontal and amacrine cells. Increases of 30% and 50%, respectively, were also observed for calretinin- and parvalbumin-positive cells in the inner nuclear layer after BDNF treatment. The retinas of bdnf −/− mice showed recoverin expression 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 upregulated in the ganglion cell layers 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.
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