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

摘要

PURPOSE: 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.