May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
D–serine as a glial–neuronal modulator in the vertebrate retina
Author Affiliations & Notes
  • R.F. Miller
    Dept of Neuroscience,
    University of Minnesota Medical School, Minneapolis, MN
  • E.R. Stevens
    Dept of Neuroscience,
    University of Minnesota Medical School, Minneapolis, MN
  • M. Esguerra
    Dept of Neuroscience,
    University of Minnesota Medical School, Minneapolis, MN
  • K.B. O'Brien
    Dept of Chemistry, University of Minnesota, Minneapolis, MN
  • M.T. Bowser
    Dept of Chemistry, University of Minnesota, Minneapolis, MN
  • K.R. Zahs
    Dept of Physiology,
    University of Minnesota Medical School, Minneapolis, MN
  • Footnotes
    Commercial Relationships  R.F. Miller, None; E.R. Stevens, None; M. Esguerra, None; K.B. O'Brien, None; M.T. Bowser, None; K.R. Zahs, None.
  • Footnotes
    Support  EY03014
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 2265. doi:
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      R.F. Miller, E.R. Stevens, M. Esguerra, K.B. O'Brien, M.T. Bowser, K.R. Zahs; D–serine as a glial–neuronal modulator in the vertebrate retina . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2265.

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

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Abstract

Abstract: : Purpose: Determine the presence, synthetic machinery and functional role of D–serine in the vertebrate retina Methods: Electrophysiological, immunohistochemical and capillary electrophoresis techniques were applied to amphibian and mammalian retinas to determine the presence of D–serine and its synthetic pathway serine racemase. The physiological actions of D–serine were studied with whole–cell and extracellular recordings in which NMDA receptor contributions were analyzed. Reduction of D–serine through exogenous application of D–amino acid oxidase was also carried out. The possible contributions of glycine to NMDA receptor sensitivity was evaluated by blocking the GlyT1 transporter with the antagonist N[3–(4–fluorophenyl)–3–(4–phenylphenoxy)–propyl]sarcosine (NFPS). Results: D–serine is abundantly present in the retina and has been localized to Muller cells and astrocytes. The synthesizing enzyme serine racemase is also found in these glial cells. Release of endogenous D–serine from the isolated amphibian retina is observed by elevating external K or in response to the application of Kainic Acid (KA); the KA–evoked release is markedly enhanced when co–applied with cyclothiazide. Muller cells show an increase in calcium generated by KA and KA/cyclothiazide, suggesting a possible mechanism for release. Exogenous D–serine enhanced NMDA responses in retinal ganglion cells, suggesting that the co–agonist site of the NMDA receptors is not saturated under our experimental conditions. Blocking the high affinity glycine transporter GlyT1, enhanced NMDA receptor currents in ganglion cells, suggesting that one role of this transporter is to keep glycine levels around NMDA receptor sites below saturation, whereas D–serine does not seem to be burdened with this restriction. It seems likely therefore that D–serine is a major modulator of NMDA receptors in the vertebrate retina and contributes to synaptic processing in the retina. Conclusions: D–serine is a newly discovered neuromodulator in the retina that subserves glial control over NMDA receptor sensitivity and hence contributes to the regulation of cell excitability and synaptic operations within the neural network of the retina.

Keywords: retina: proximal (bipolar, amacrine, and ganglion cells) • signal transduction • Muller cells 
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