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Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rd1 mouse retina

Delyfer, MN; Forster, V; Neveux, N; Picaud, S; Leveillard, T; Sahel, JA; (2005) Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rd1 mouse retina. Molecular vision , 11 688 -696. Green open access

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Abstract

PURPOSE: Kinetic studies of photoreceptor cell death in the retinal degeneration (rd1) mouse model suggest that photoreceptor degeneration could result from cumulative damage. Since alterations in glutamate metabolism have been described in different models of retinitis pigmentosa, we investigated in the present work whether changes in glutamate turnover occur in the degenerating rd1 retina and whether glutamate-mediated excitotoxic mechanisms may contribute to rod photoreceptor death in this model. METHODS: Free amino acid levels were quantified in rd1 and wild-type retinas using an amino acid analyzer selecting times corresponding to early, intermediate, and terminal phases of rod photoreceptor degeneration. Reverse transcription-polymerase chain reaction (RT-PCR) was used to compare the mRNA expression levels of the glial L-glutamate/L-aspartate transporter GLAST, glutamine synthetase (GS), and vimentin, a marker for retinal glia, between rd1 and wild-type mouse retinas. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an antagonist of both AMPA and kainate subtypes of ionotropic glutamate receptors, was then daily administered from postnatal day 3 (PN3) to PN21 to rd1 mice while control rd1 mice received only physiological saline solution (7 per treatment). At PN22, the respective numbers of surviving rods in

Type: Article
Title: Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rd1 mouse retina
Open access status: An open access version is available from UCL Discovery
Publisher version: http://www.molvis.org/molvis/volume11.html
Language: English
Additional information: This work is licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivativeWorks 3.0 license. You are free to share (copy, distribute and transmit the work), but you must attribute the author, you may not use this work for commercial purposes and you may not alter, transform, or build upon this work and distribute any derivative works you create under a similar license.
Keywords: Cell death, Metabolism, Methods, Mice, Mouse, Mouse Retina, photoreceptor, Retina, Retinal degeneration, Retinitis, Retinitis pigmentosa, Rod
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/40011
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