NMDA model
One of the animal models is based on the effect of glutamate. Glutamate has several functions [1], but in the neurological system it is an important neurotransmitter [2]. However, high quantities of glutamate have a destructive role in many neurodegenerative diseases, like Morbus Parkinson [3], Morbus Alzheimer [4] or glaucoma [5]. It is known that glutamate is involved in the degeneration mechanisms in high pressure [6] and normal pressure models of glaucoma [7]. To investigate the direct pathological effect of glutamate on the neurons, an established rat retinal degeneration model was used. Therefore, N-Methyl-D-Aspartate (NMDA), a synthetic glutamate analogue, was intraocular injected to induce a very fast retinal degeneration [8]. Studies showed that the first cells undergo apoptotic processes after 12 hours [9]. The advantage of the NMDA over glutamate is a slower degradation, and for this reason, a longer activation of the NMDA receptor. The aims of this experiment are to investigate the pathological alterations of retina and optic nerves and the immunological reaction, especially of the glia cells, at a late point in time. In a pilot project, we detected that the retinal ganglion cells declined significantly three days after the NMDA injection. Usually, the activation of the retinal microglia is only an early response during the degeneration processes [10]. Yet, we noted that the microglia were not only activated three days after the injection, but also after 14 days [11]. An unknown mechanism led to a long-lasting activation of the microglia in this model. These mechanisms need further analysis.
Conference contributions
Rodust C, Kuehn S, Stute G, Dick HB, Joachim SC. Cell death in retina and optic nerve in a NMDA-induced retina degeneration model. Deutsche Ophthalmologische Gesellschaft, 2015.
Rodust C, Kuehn S, Stute G, Dick HB, Joachim S. Activation of microglia in a NMDA-induced retinal damage model. Deutsche Ophthalmologische Gesellschaft; 2014.
Kuehn S, Rodust C, Stute G, Dick HB, Joachim SC. Modulation of microglia response in an N-Methyl-D-Aspartat induced neurodegeneration model. Gesellschaft für Biochemie und Molekularbiologie, Bochum; 2014.
Rodust C, Kuehn S, Stute G, Dick HB, Joachim SC. Konzentrationsabhängige Aktivierung von Mikroglia in NMDA-Degenerationsmodell. Jahrestagung der Rheinisch-Westfälischen Augenärzte; 2015.
Literature
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[5] Dreyer EB, Zurakowski D, Schumer RA, Podos SM, Lipton SA. Elevated glutamate levels in the vitreous body of humans and monkeys with glaucoma. Archives of ophthalmology, 1996;114:299-305.
[6] Kim JH, Lee NY, Jung SW, Park CK. Expression of N-methyl-d-aspartate receptor 1 in rats with chronic ocular hypertension. Neuroscience, 2007;149:908-16.
[7] Namekata K, Harada C, Guo X, Kikushima K, Kimura A, Fuse N et al. Interleukin-1 attenuates normal tension glaucoma-like retinal degeneration in EAAC1-deficient mice. Neurosci Lett, 2009;465:160-4.
[8] Seitz R, Tamm ER. N-methyl-D-aspartate (NMDA)-mediated excitotoxic damage: a mouse model of acute retinal ganglion cell damage. Methods Mol Biol, 2013;935:99-109.
[9] Manabe S, Lipton SA. Divergent NMDA signals leading to proapoptotic and antiapoptotic pathways in the rat retina. Invest Ophthalmol Vis Sci, 2003;44:385-92.
[10] Bosco A, Steele MR, Vetter ML. Early microglia activation in a mouse model of chronic glaucoma. J Comp Neurol, 2011;519:599-620.
[11] Kuehn S, Rodust C, Stute G, Dick HB, Joachim SC. Modulation of microglia response in an N-Methyl-D-Aspartat induced neurodegeneration model. Gesellschaft für Biochemie und Molekularbiologie, Bochum; 2014.