March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Synaptic Localization of D-Amino Acid Oxidase in the Mouse Retina
Author Affiliations & Notes
  • Catherine W. Morgans
    Casey Eye Institute, Oregon Health & Science Univ, Portland, Oregon
  • Manuel Esguerra
    Neuroscience, University of Minnesota, Minneapolis, Minnesota
  • Robert F. Miller
    Neuroscience, University of Minnesota, Minneapolis, Minnesota
  • Footnotes
    Commercial Relationships  Catherine W. Morgans, None; Manuel Esguerra, None; Robert F. Miller, None
  • Footnotes
    Support  NIH NEI R01 EY03014
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 4324. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Catherine W. Morgans, Manuel Esguerra, Robert F. Miller; Synaptic Localization of D-Amino Acid Oxidase in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4324.

      Download citation file:

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

  • Supplements

Purpose: : In the retina, D-serine has been shown to be the predominant co-agonist of NMDA receptors (NMDARs). The co-agonist site is unsaturated under physiological conditions, and modulation of D-serine levels dramatically affects the light responses of retinal ganglion cells. The local concentration of D-serine is determined by the activity and localization of the enzymes that synthesize, degrade and transport D-serine. We show that the D-serine degrading enzyme, D-amino acid oxidase (DAO), is synaptically localized in the retina.

Methods: : A linked DAO-HRP activity assay was performed on lightly fixed retinal sections from wild-type mice and from mice with a loss-of-function point mutation (G181R) in the DAO gene, ddY/DAO- mice. DAO was localized in wildtype and ddY/DAO- retina sections by immunofluorescence and confocal microscopy. Some sections were double labeled with antibodies against DAO and NMDAR subunits, or against DAO and synaptic ribbon proteins to identify sites of glutamate release.

Results: : The DAO assay localized enzymatic activity to the inner plexiform layer (IPL) in the wild-type retina but not in the ddY/DAO- mutant retina. The location of the reaction product corresponded to the localization of DAO immunofluorescence. In both wildtype and ddY/DAO- retina sections, the DAO antibody labeled dense puncta throughout the IPL, indicating that the ddY/DAO- point mutation affects function but not localization of the enzyme. Double labeling revealed close apposition of DAO and NMDARs, as well as synaptic ribbons.

Conclusions: : The localization of DAO in the IPL suggests that modulation of DAO activity in the retina will affect synaptic D-serine levels, and hence ganglion cell light responses.

Keywords: excitatory amino acid receptors • retina: proximal (bipolar, amacrine, and ganglion cells) • neurotransmitters/neurotransmitter systems 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.