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Int J Ophthalmol. 2018 Nov 18;11(11):1746-1754. doi: 10.18240/ijo.2018.11.03. eCollection 2018.

Exploration of the glutamate-mediated retinal excitotoxic damage: a rat model of retinal neurodegeneration.

Author information

1
Department of Ophthalmology, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing 400042, China.
2
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Research Institute of Surgery and Daping Hospital, Army Medical University, Chongqing 400042, China.

Abstract

AIM:

To explore the more suitable concentration of glutamate or N-methyl-D-aspartic acid (NMDA) for intravitreal injection to establish a rat model of retinal neurodegeneration.

METHODS:

We injected different doses of glutamate (20 or 50 nmol) or NMDA (40 nmol) into the vitreous chambers of rats, then measured the concentration of glutamate and retinal thickness, quantified apoptotic cells and determined the degree of tau hyperphosphorylation at different time points. T-test was used for comparison of two groups. One-way ANOVA and Turkey's multiple comparisons test were used for comparisons of different groups, and P values below 0.05 were considered statistically significant.

RESULTS:

The glutamate level in the rats treated with 50 nmol of glutamate was twice that of the control group and persisted two weeks. Seven days after intravitreal injection of 50 nmol of glutamate, three parameters [inner retinal thickness (IRT), retinal thickness (RT) and ganglion cell layer (GCL) cell number] were reduced significantly. Furthermore, numerous TUNEL-positive cells were observed in the GCL one day after intravitreal injection of 50 nmol of glutamate, the expression of the apoptosis-related factor cleaved casepase-3 was markedly increased compared with the expression levels in the other treatment groups, and the expression levels of tau s396 and tau s404 were significantly increased compared with those in the control group.

CONCLUSION:

This study demonstrates that the intravitreal injection of 50 nmol of glutamate can establish the more effective retinal neurodegeneration animal model relative to other treatment groups.

KEYWORDS:

animal model; excitotoxicity; glaucoma; glutamate; retinal neurodegeneration

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