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B. Belachew, R. Purgert, J. DeBrecht, E. Barr, P. Lukasiewicz, M. Brantley; Abnormal Outer Plexiform Signaling in Neurturin Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1045.
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© ARVO (1962-2015); The Authors (2016-present)
Neurturin, a member of the GDNF family of ligands, is a neurotrophic factor important in retinal survival. Its absence in knockout mice (NTRN-/-) results in significant structural and functional abnormalities in the retina, including mislocalized bipolar cell dendritic processes in the outer plexiform layer (OPL) and markedly reduced photopic and scotopic ERG responses. The purpose of this study was to evaluate the synaptic basis of this functional abnormality and determine whether it stems from a disruption of pre- or postsynaptic signaling.
Whole cell patch clamp recordings were made from retinal slices of WT and NTRN-/- mice. Recordings were obtained from three classes of bipolar cells (BCs) (rod, on cone and off cone BCs), which were morphologically identified using sulfarhodamine dye in the recording electrode. The BCs were stimulated by a puff of AP4/kainate mixture onto their dendrites. OPL structure was analyzed by labeling pre- and post-synaptic elements, in WT and NTRN-/- retinas with antibodies to RIBEYE and PKC, respectively.
Bipolar cell responses were recorded from 29 WT and 28 NTRN-/- mice. Data analysis showed no significant difference in the conductance of any of the three types of BCs between WT and NTRN-/- mice. These results support the hypothesis that the abnormality in synaptic signaling of neurturin deficient mice is attributable to a pre-synaptic defect since post-synaptic BC responses were similar to WT. Morphologic analysis revealed abnormal BC processes in the OPL of NTRN-/- mice associating with ectopic presynaptic ribbon elements. These findings corroborate the pre-synaptic basis of the retinal dysfunction in neurturin deficiency.
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