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Memantine protects neurons from shrinkage in the lateral geniculate nucleus in experimental glaucoma.

Yücel YH, Gupta N, Zhang Q, Mizisin AP, Kalichman MW, Weinreb RN

Department of Ophthalmology and Vision Sciences, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. yeni.yucel@utoronto.ca

OBJECTIVE: To determine whether memantine as a treatment for glaucoma prevents neuron shrinkage in the lateral geniculate nucleus, the major target for retinal ganglion cells. METHODS: Sixteen monkeys with right-eye unilateral experimental glaucoma for 14 months were studied and treated with memantine (n = 9) or vehicle only (n = 7). Left lateral geniculate nucleus relay neurons (layers 1, 4, and 6) were examined following parvalbumin immunolabeling. Cell body cross-sectional areas and neuron numbers were assessed using unbiased methods. Memantine- and vehicle-treated glaucoma groups were compared using t tests and analysis of covariance. RESULTS: Compared with vehicle-treated animals, memantine-treated animals showed significantly less mean +/- SD neuron shrinkage in layers 1 (-4.0% +/- 13.9% vs 28.2% +/- 17.4%; P = .001) and 4 (24.9% +/- 10.0% vs 37.2% +/- 12.3%; P = .04). For layer 6, the difference was not statistically significant (34.2% +/- 10.1% vs 45.3% +/- 14.5%; P = .10). Analysis of covariance results showed significantly less neuron shrinkage in the memantine-treated group for layers 1, 4, and 6 (P < .001; P < .02; and P < .04, respectively). This difference was greatest in layer 1. In each of these layers, neuron numbers did not differ significantly between groups. CONCLUSION: Monkeys with glaucoma that were treated with memantine showed significantly less neuron shrinkage in the lateral geniculate nucleus than the vehicle-treated glaucoma group. CLINICAL RELEVANCE: The finding that memantine protects adult visual neurons from transsynaptic atrophy in experimental glaucoma could have therapeutic value. Currently, memantine is being tested in an ongoing clinical trial as a treatment for glaucoma.

Published 14 February 2006 in Arch Ophthalmol, 124(2): 217-25.
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