Memantine Protects Lateral Geniculate Neurons From Shrinkage in the Glaucoma Brain

Abstract

Abstract: : Purpose:To determine whether memantine, a NMDA open channel blocker, prevents neuron shrinkage in glaucoma in the lateral geniculate nucleus (LGN), the major target for retinal ganglion cells. Methods:Sixteen monkeys with right eye unilateral experimental glaucoma were studied, treated with memantine (n=9) and vehicle only (n=7). Left LGN relay neurons (layers 1, 4, 6) were studied following parvalbumin immunolabelling. Cell body cross–sectional areas and neurons numbers were assessed using unbiased stereological methodology. Memantine and vehicle–treated glaucoma groups were compared using t–tests, and analysis of covariance (ANCOVA) tests. Using generalized linear models procedure of Statistical Analysis Software (SAS, Cary, NC), neuron shrinkage was regressed separately on % optic nerve fiber loss. Treatment was added as a factor for analysis of covariance. Results:Compared to vehicle–treated animals, memantine–treated animals showed significantly less mean neuron shrinkage in layers 1 and 4 (–4.0 ± 13.9 % vs. 28.2 ± 17.4 %; P= 0.001), (24.9 ± 10.0 % vs. 37.2 ± 12.3 %; P=0.044), respectively. For layer 6, this difference was not statistically significant (34.2 ± 10.1 % vs. 45.3 ± 14.5 %; P= 0.0946). ANCOVA tests showed significantly less neuron shrinkage in the memantine–treated group for all layers (layer 1, P=0.0002), (layer 4, P=0.0176) and (layer 6, P=0.0349). In each of these layers, neuron numbers did not differ significantly between groups. Conclusions: Memantine protects lateral geniculate nucleus neurons from shrinkage following glaucomatous optic nerve injury. These findings implicate NMDA excitotoxicity in the pathobiology of degenerative changes in the brain in glaucoma.

Keywords: neuroprotection • pathology: experimental • thalamus/lateral geniculate nucleus