Memantine Protects Neurons From Shrinkage in the Lateral Geniculate Nucleus in Experimental Glaucoma

Abstract

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 (PϽ.001; PϽ.02; and PϽ.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 vehicletreated 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.

Evaluation of corpus geniculatum laterale and vitreous fluid by magnetic resonance spectroscopy in patients with glaucoma; a preliminary study

“…Therefore, it is argued that the neuroprotective agents can be used in the therapy of glaucoma. A study, conducted by Yucel et al 21 on nine monkeys with experimentally created glaucoma, showed that the use of memantine, which is a NMDA receptor blocker, gave better statistically significant results when compared with controls in neuronal damage and neuron atrophy in the LGB region.…”

Dosage dependence of the effect of Ginkgo biloba on the rat retinal ganglion cell survival after optic nerve crush

“…It has, therefore, been desirable to develop treatment strategies by which the retina and optic nerve can be protected from degeneration by helping the retinal cells to survive even under difficult conditions. Recent studies have reported that substances such as ciliary neurotrophic factor, [3][4][5] brain-derived growth factor, 6 memantine, 7,8 and Ginkgo biloba may have a stabilizing or protecting effect on retinal cells in experimental conditions. [9][10][11][12][13][14][15][16][17][18][19][20][21][22] Particularly for Ginkgo biloba, potential antioxidant functions have been discussed to be helpful for impaired retinal cells such as Mü ller cells.…”

Gantrez AN Nanoparticles for Ocular Delivery of Memantine: In vitro Release Evaluation in Albino Rabbits

“…Memantine is used in the treatment of Parkinson’s disease, some types of movement disorders [19] and some dementia syndromes [20], and has recently been described as a potential treatment for glaucoma [21]. …”