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Functional protective effects of long-term memantine treatment in the DBA/2J mouse

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Abstract

Purpose

To analyse the effects of long-term memantine treatment on the retinal physiology and morphology of DBA/2J mice.

Methods

DBA/2J (D2J) mice received i.p. injections of the NMDA receptor antagonist memantine, which protects neurons from abnormally elevated glutamate levels, twice a day over a period of 7 months. At the age of 2, 6 and 10 months, the intraocular pressure (IOP) and electroretinograms (ERGs) were measured in all treated D2J mice, in untreated D2J controls and in C57Bl/6 (B6) wild-type mice. After the last measurement at the age of 10 months, the mice were killed and the retinae and the optic nerves were analysed morphologically.

Results

The IOP increased with age in both D2J and B6 mice with a larger increase in the D2J strain. IOPs were not influenced by memantine treatment. The response amplitude of the scotopic flash ERG decreased with age in the D2J strain. This amplitude decrease, particularly that of the b-wave, was smaller in treated D2J mice. The retinae of treated D2J mice exhibited less peripheral degeneration of cone photoreceptors, and optic nerve neuropathy was less frequent.

Conlcusions

Application of the NMDA receptor antagonist memantine diminished retinal neurodegeneration in the D2J mice and had a protective effect on the b-wave amplitude of the scotopic flash ERG. This protection may occur secondarily as memantine primarily acts on retinal ganglion cells.

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Acknowledgments

The work was supported by Novartis Institutes for BioMedical Research. JK is supported by the Excellence Program of the Hertie Foundation. MS is supported by the Johannes und Frieda Marohn Foundation, Erlangen.

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Authors and Affiliations

  1. Department of Ophthalmology, University Hospital Erlangen, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany

    Jenny Atorf & Jan Kremers

  2. Institute of Anatomy II, University of Erlangen-Nuremberg, Universitätsstr. 19, 91054, Erlangen, Germany

    Michael Scholz, Fabian Garreis, Julia Lehmann & Lars Bräuer

  3. Rhenovia Pharma, Mulhouse, France

    Jan Kremers

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  1. Jenny Atorf
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  2. Michael Scholz
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Correspondence to Michael Scholz.

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Jenny Atorf, Michael Scholz contributed equally to this work.

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Atorf, J., Scholz, M., Garreis, F. et al. Functional protective effects of long-term memantine treatment in the DBA/2J mouse. Doc Ophthalmol 126, 221–232 (2013). https://doi.org/10.1007/s10633-013-9380-3

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  • DOI: https://doi.org/10.1007/s10633-013-9380-3

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