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Memantine Protects Neurons From Shrinkage in the Lateral Geniculate Nucleus in Experimental Glaucoma
Yeni H. Yücel, MD, PhD, FRCPC;
Neeru Gupta, MD, PhD, FRCSC;
Qiang Zhang, PhD;
Andrew P. Mizisin, PhD;
Michael W. Kalichman, PhD;
Robert N. Weinreb, MD
Arch Ophthalmol. 2006;124:217-225.
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.
Author Affiliations: Departments of Ophthalmology and Vision Sciences (Drs Yücel and Gupta) and Laboratory Medicine and Pathobiology (Drs Yücel and Gupta), the Health Sciences Research Center (Drs Yücel, Gupta, and Zhang), and Glaucoma and Nerve Protection Unit (Dr Gupta), St Michael's Hospital, University of Toronto, Toronto, Ontario; Departments of Pathology (Drs Mizisin and Kalichman) and Ophthalmology (Dr Weinreb) and the Hamilton Glaucoma Center (Dr Weinreb), University of California, San Diego.
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