Efficacy and safety of memantine treatment for reduction of changes associated with experimental glaucoma in monkey, II: Structural measures.
OBJECTIVE
To determine, using anatomic measurements, whether daily oral dosing with memantine is both safe and effective to reduce the injury associated with experimental glaucoma in primates.


METHODS
Argon laser treatment of the anterior chamber angle was used to induce chronic ocular hypertension (COHT) in the right eyes of 18 macaque monkeys. Nine animals were daily orally dosed with 4 mg/kg memantine while the other nine animals received vehicle only. Measurements of intraocular pressure (IOP) from both eyes of all animals were made at regular intervals. Appearance of the optic nerve head, retinal vessels, and surrounding retina was documented with stereo fundus photographs obtained at multiple time points throughout the study. Measurements of optic nerve head topography were obtained from confocal laser scans made from animals with the highest IOPs at approximately 3, 5, and 10 months after elevation of IOP. At approximately 16 months after IOP elevation, animals were killed and histologic counts of cells in the retinal ganglion cell (RGC) layer were made.


RESULTS
Histologic measurements showed that, for animals with moderate elevation of IOP, memantine treatment was associated with an enhanced survival of RGCs in the inferior retina. Measurements of optic nerve head topography showed less IOP-induced change in memantine-treated animals. This effect was seen in measurements of both the cup and the neuroretinal rim. A comparison of these same histologic and morphologic measurements in normotensive eyes from the two treatment groups showed that memantine treatment was not associated with any significant effects on these eyes.


CONCLUSIONS
Histologic measurements of RGC survival as well as tomographic measurements of nerve head topography show that systemic treatment with memantine, a compound which does not lower intraocular pressure, is both safe and effective to reduce changes associated with experimental glaucoma.
Department of Biological Sciences, Allergan Inc., Irvine, California 92612, USA. hare_william@allergan.com
William A
WA
Hare
Elizabeth
E
WoldeMussie
Robert N
RN
Weinreb
Hau
H
Ton
Guadalupe
G
Ruiz
Mercy
M
Wijono
Barbara
B
Feldmann
Linda
L
Zangwill
Larry
L
Wheeler
D000284:Administration, Oral; D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005901:Glaucoma / Q000188:drug therapy* / Q000473:pathology; D007429:Intraocular Pressure; D008252:Macaca fascicularis; D008559:Memantine / Q000008:administration & dosage / Q000627:therapeutic use*; D009798:Ocular Hypertension / Q000188:drug therapy / Q000473:pathology; D009898:Optic Disk / Q000473:pathology*; D009901:Optic Nerve Diseases / Q000188:drug therapy / Q000473:pathology; D012160:Retina / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D012449:Safety; D016896:Treatment Outcome
D018691:Excitatory Amino Acid Antagonists; D008559:Memantine