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Michal Fiedorowicz, Jaroslaw Orzel, Bartosz Kossowski, Marlena Welniak-Kaminska, Piotr Bogorodzki, Pawel Grieb; Metabolic hallmarks of visual cortex neurodegeneration in DBA/2J mouse model of glaucoma, a proton magnetic resonance spectroscopy study. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2451.
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© ARVO (1962-2015); The Authors (2016-present)
Recent data show that glaucoma affects extra-retinal vision-related brain structures (including visual cortex) but dynamics and mechanisms of this degeneration remain unclear. We hypothesize that visual cortex neurodegeneration in experimental glaucoma (DBA/2J mice) is more pronounced than in other areas of cerebral cortex and is related to extensive glutamate toxicity.
DBA/2J mice (18 months of age, n=10) and age matched C57Bl/6 mice (n=10) that served as controls were anaesthetized with isoflurane and placed in 7T small animal-dedicated magnetic resonance tomograph (BioSpec 70/30USR; Bruker BioSpin, Ettlingen, Germany). In order to obtain in vivo proton MR spectra two distinct voxels of interests (VOIs) corresponding to visual cortex (5x2x1.2 mm3) and frontal cortex (4x2x1.5mm3) were precisely positioned basing on T2-weighted images. Spectra were obtained with PRESS sequence (TR=2000ms, TE=20ms, NA=1024, Scan time=34min). The data were analyzed with LCModel software (Stephen Provencher Inc, Oakville, Ontario, Canada). Spectra of poor quality (SNR ratio < 15) were excluded from further analysis.Metabolite concentrations are reported as ratios to total creatine (sum of creatine and phosphocreatine peaks, tCr). Statistical analysis was performed with U Mann-Whitney test.
Taurine to tCr ratio was significantly lower in DBA/2J mice than in controls in the visual cortex (0.820±0.021 vs. 0.959±0.022, P<0.001) but not in the frontal cortex (1.084±0.021 vs. 1.169±0.033, ns.). Glutamate to tCr ratio was significantly higher (1.081±0.017 vs. 1.005±0.029, P<0.05) in the visual cortex of DBA/2J mice than in the control mice, while no significant difference was observed in the frontal cortex (1.257±0.028 vs. 1.297±0.044, ns.). Glutamine to tCr ratio was lower in DBA/2J than in C57Bl/6 mice in visual cortex (0.442±0.031 vs. 0.608±0.071, P<0.05) and in frontal cortex (0.533±0.025 vs. 0.690±0.058, P<0.05). No significant differences were detected for N-acetylaspartate and total choline.
Changes in metabolite concentrations indicate a neurodegenerative process that affects visual cortex in DBA/2J mouse model of glaucoma. Increase in glutamate signal support the hypothesis that this neurodegeneration is mediated by excitotoxicity.
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