April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
AMPA Receptor Activation Induces D-serine Release in the Mouse Retina
Author Affiliations & Notes
  • S. J. Sullivan
    Neuroscience, University of Minnesota, Minneapolis, Minnesota
  • M. Esguerra
    Neuroscience, University of Minnesota, Minneapolis, Minnesota
  • R. F. Miller
    Neuroscience, University of Minnesota, Minneapolis, Minnesota
  • Footnotes
    Commercial Relationships  S.J. Sullivan, None; M. Esguerra, None; R.F. Miller, None.
  • Footnotes
    Support  NIH Grants: EY03014 to RFM & T32 EY07133 for support of SJS
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 1030. doi:
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      S. J. Sullivan, M. Esguerra, R. F. Miller; AMPA Receptor Activation Induces D-serine Release in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1030.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : NMDA receptors (NMDARs) located on retinal ganglion cells (RGCs) contribute to light evoked responses. Glutamate activation of NMDARs requires a coagonist, either glycine or D-serine. D-serine and its synthesizing enzyme serine racemase are primarily localized to retinal glia, and evidence suggests that D-serine is the primary coagonist for NMDARs. However, little is known about D-serine release in the retina. To overcome some of the difficulties in measuring retinal D-serine, we have utilized a mutant mouse lacking function D-amino acid oxidase (DAO-), which has elevated D-serine, to explore the possibility that D-serine release is induced by AMPA receptor (AMPAR) activation.

Methods: : D-serine measurement: Amino acids were isolated from the retina and fluorescently tagged with NBDF for laser induced detection. Samples were separated via capillary electrophoresis and a cyclodextrin-containing buffer allowed for separation of enantiomeric amino acids.Calcium imaging: Ca2+ changes in isolated mouse retinas loaded with Fluo-4 were measured using a multiphoton imaging system.

Results: : D-serine measurement: DAO- retinas had significantly more tissue and extracellular D-serine when compared to wt controls. AMPA and cyclothiazide together induced D-serine release in both mice but this effect was exaggerated in DAO- mice. In DAO- mice, D-serine release was attenuated by N-acetyl spermine (NAS), a Ca2+ permeable AMPAR antagonist. Elevating extracellular glutamate by blocking glutamate transporters resulted in D-serine release only when cyclothiazide was co-applied and this effect was blocked by an AMPAR antagonist.Calcium imaging: AMPA and cyclothiazide treatment of whole-mount retinas elevated Ca2+ in in glial cells and this response was significantly reduced by NAS.

Keywords: retinal glia • receptors • neurotransmitters/neurotransmitter systems 

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