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T. Ly, N. Gupta, A. Darabie, R. N. Weinreb, Y. Yucel; Memantine Treatment in Chronic Ocular Hypertension Increases Dendrite Complexity of Neurons in the Lateral Geniculate Nucleus. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5500. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the effect of memantine, an NMDA open channel blocker, on dendrite complexity of lateral geniculate nucleus (LGN) magno- and parvocellular neurons in primate chronic ocular hypertension.
Macaque monkeys with right eye ocular hypertension for 14 months with minimal to no optic nerve fiber loss, treated with daily memantine 4mg/kg (n=5) were compared to vehicle-treated ocular hypertensive animals (n=4). Mean intraocular pressure (±SD) for memantine-and vehicle-treated groups was 31.3 ± 4.4 mmHg and 34.4 ± 5.8 mmHg, P> 0.05, and mean % optic nerve fiber loss was 5.80 ± 8.93 % and 11.8 ± 13.9 %; P> 0.05, respectively. LGN sections were double-immunostained for microtubule-associated protein-2 (MAP-2), a dendrite marker, and for parvalbumin, a relay neuron marker. Confocal image stacks (18 µm thick) were collected with 488nm and 543nm excitation. Dendrites of relay neurons in left LGN magnocellular layer 1 and parvocellular layer 6 were traced (AutoNeuron, MicroBright Field Inc, VT) and three-dimensionally reconstructed. (3D Solid Views, MicroBright Field Inc, VT). In a masked fashion, dendrite complexity was evaluated by Sholl analysis for each neuron with morphometric software (Neurolucida, MicroBrightField Inc, VT). Dendrite complexity in the memantine-treated group was compared to those in the vehicle-treated group using a two-tailed t-test.
Magnocellular neurons in the memantine-treated ocular hypertensive group showed significantly greater dendrite complexity, compared to the vehicle-treated ocular hypertensive group (16.3 ± 1.4 vs. 11.7 ± 0.8 (mean ± SD); P < 0.001).Parvocellular neurons in the memantine-treated group showed significantly greater dendrite complexity compared to the vehicle- treated group (14.9 ± 1.1 vs. 11.9 ± 0.90; P < 0.005).
In chronic primate ocular hypertension with minimal optic nerve damage, memantine showed a protective effect on dendrite complexity in LGN neurons. As dendrite arborisation is critical to visual signal processing, this finding may be relevant to the prevention of vision dysfunction and loss in glaucoma.
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