Exogenous brain-derived neurotrophic factor (BDNF) reverts phenotypic changes in the retinas of transgenic mice lacking the BDNF gene.
OBJECTIVE
The authors investigated the effect of brain-derived neurotrophic factor (BDNF) administration on the expression of Ca(2+)-binding proteins in the developing bdnf(-/-) mouse retina.


METHODS
Intraocular injections of BDNF (0.5 microg) were applied on postnatal day (P) 11 bdnf(-/-) mice, and their effects were evaluated on P14. Neurons expressing Ca(2+)-binding protein were studied by immunohistochemistry for PKC-alpha, recoverin, calbindin-D28K, calretinin, and parvalbumin.


RESULTS
Cell density and immunostaining intensity for Ca(2+)-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 Ca(2+)-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.
Arango-González
Blanca
B
Division of Experimental Ophthalmology, Centre for Ophthalmology, Tübingen, Germany.
Cellerino
Alessandro
A
Kohler
Konrad
K
D025042:Amacrine Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D064092:Calbindin 1; D064032:Calbindin 2; D064026:Calbindins; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002452:Cell Count; D015536:Down-Regulation; D020868:Gene Silencing / Q000502:physiology; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D010320:Parvalbumins / Q000378:metabolism; D010641:Phenotype; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051603:Recoverin / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D051248:Retinal Horizontal Cells / Q000166:cytology / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; C576499:Calb1 protein, mouse; C576511:Calb2 protein, mouse; D064092:Calbindin 1; D064032:Calbindin 2; D064026:Calbindins; D002135:Calcium-Binding Proteins; D010320:Parvalbumins; C496732:Rcvrn protein, mouse; D064030:S100 Calcium Binding Protein G; D051603:Recoverin; D051571:Protein Kinase C-alpha