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.