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Alterations of amino acids and glutamate transport in the DBA/2J mouse retina; possible clues to degeneration

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Abstract

Background

The DBA/2J mouse spontaneously develops ocular hypertension and time-dependent progressive retinal ganglion cell (RGC) loss. This study examines changes in amino acid levels in the vitreous, and changes in the expression of retinal glutamate transporters and receptors that occur during the progression of this pathology.

Methods

Retinas were obtained from DBA/2J mice at ages 3, 6 and 11 months. C57BL/6 mice were used as age-matched controls. Vitreal amino acid content was measured with HPLC. Western blotting and immunohistochemistry were performed using specific antibodies against the glutamate transporters (GLAST, GLT-1v, EAAC-1) and glutamate receptors, particularly NMDA (NR1, NR2A, NR2B) and AMPA (GluR1, GluR2/3, GluR4) receptors.

Results

HPLC showed retinal concentrations of glutamate, glutamine, glycine, alanine, lysine, serine, and arginine to be significantly higher in DBA/2J mice at 11 months of age compared to age-matched controls. Western Blots revealed a moderate decrease of GLAST and GLT-1v expression in DBA/2J mice at 6 and 11 months as compared to age-matched controls while there was no change in EAAC1. Immunohistochemically, no changes in expression of NMDA and AMPA receptors were seen.

Conclusion

Alterations of amino acid content and enhanced glutamate neurotransmission might be involved in the pathogenesis of retinal neurodegeneration in the DBA/2J mouse model of ocular hypertension. Moreover, these mice provide an animal model for studying excitotoxic retinal damage.

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Acknowledgements

Frank Schuettauf was supported by the fortüne program (912-1-0) and the European Union (QLK6-CT-2001-00385). Dr. med. Robert Rejdak was supported by the Kerstan Foundation and European Union under a Marie Curie Individual Fellowship (QLK2-CT-2002-51562).The authors gratefully thank Prof. Kugler for providing an antibody directed at a splice variant of GLT1v for this study, Dr. Rita Naskar and Ephraim Lessell for numerous helpful comments, Sandra Bernhard-Kurz and Tomasz Choragiewicz for excellent technical assistance.

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Authors and Affiliations

  1. Department of Pathophysiology of Vision and Neuro-Ophthalmology, University Eye Hospital, Schleichstrasse 12, 72076, Tübingen, Germany

    Frank Schuettauf, Sebastian Thaler, Sylvia Bolz, Julia Fries, Eberhart Zrenner & Robert Rejdak

  2. Medizinisch-Naturwissenschaftliches Forschungszentrum, Tübingen, Germany

    Hubert Kalbacher

  3. Tadeusz Krwawicz Chair of Ophthalmology and 1st Eye Hospital, Medical University, Lublin, Poland

    Anna Mankowska & Robert Rejdak

  4. Departments of Orthopaedic Surgery and Biostatistics, Children’s Hospital, Harvard Medical School, Boston, MA, USA

    David Zurakowski

  5. Medical Research Centre, Polish Academy of Science, Warsaw, Poland

    Robert Rejdak

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  1. Frank Schuettauf
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Correspondence to Frank Schuettauf.

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Schuettauf, F., Thaler, S., Bolz, S. et al. Alterations of amino acids and glutamate transport in the DBA/2J mouse retina; possible clues to degeneration. Graefes Arch Clin Exp Ophthalmol 245, 1157–1168 (2007). https://doi.org/10.1007/s00417-006-0531-z

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  • DOI: https://doi.org/10.1007/s00417-006-0531-z

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