This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Glutamate is the main excitatory neurotransmitter in the retina, used along the visual pathway from rods and cones to bipolar cells, and from these to ganglion cells and to the brain. Glutamate stimulates two classes of receptors: ionotropic ligand-gated channels and G protein-coupled mGluRs. Group-III mGluRs are a subset of related mGluRs selectively activated by L-2-amino-4-phosphonobutyric acid (APB) and consist of mGluR4, -R6, -R7, and -R8. Except for mGluR6, which mediates the depolarizing response of ON-bipolar cells to light, the function of the other mGluRs in the retina remains undefined. We found that mGluR4, -R7, and -R8 are localized within the proximal retina. Retinal function may be assessed in-vivo with the electroretinogram (ERG), a measure of the change in voltage across the retina in response to light recorded from corneal electrode.
The aim of the current research was to determine the role of group-III mGluRs in inner retinal signaling as measured with the ERG. The proteins and receptors involved in G-protein signaling in rod photoreceptors are now known in detail and defects in both have been associated with visual defects in humans. A better understanding of the signaling pathway within the inner retina should provide greater insight into the causes of other visual defects. This knowledge would pave the way for development of new therapies for previously untreatable visual diseases. We found that mGluR4 deficient mice have abnormal photopic ERGs, with larger and more prolonged oscillatory potentials. We propose that the mGluR4 receptor modulates feedback from amacrine to bipolar cells.
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