Exogenous Brain-Derived Neurotrophic Factor (BDNF) Reverts Phenotypic Changes in the Retinas of Transgenic Mice Lacking the bdnf Gene

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 mu g) 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-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 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. (Invest Ophthalmol Vis Sci. 2009; 50: 1416-1422) DOI: 10.1167/iovs.08-2244