title: Glioprotection of Retinal Astrocytes After Intravitreal Administration of Memantine in the Mouse Optic Nerve Crush Model.
abstract: BACKGROUND In glaucoma, non-intraocular pressure (IOP)-related risk factors can result in increased levels of extracellular glutamate, which triggers a cascade of neurodegeneration characterized by the excessive activation of N-methyl-D-aspartate (NMDA). The purpose of our study was to evaluate the glioprotective effects of memantine as a prototypic uncompetitive NMDA blocker on retinal astrocytes in the optic nerve crush (ONC) mouse model for glaucoma. MATERIAL AND METHODS Optic nerve crush was performed on all of the right eyes (n=8), whereas left eyes served as contralateral healthy controls (n=8) in Balb/c/Sca mice. Four randomly assigned mice received 2-µl intravitreal injections of memantine (1 mg/ml) after ONC in the experimental eye. One week after the experiment, optic nerves were dissec-ted and stained with methylene blue. Retinae were detached from the sclera. The tissue was immunostained. Whole-mount retinae were investigated by fluorescent microscopy. Astrocyte counts for each image were performed manually. RESULTS Histological sections of crushed optic nerves showed consistently moderate tissue damage in experimental groups. The mean number of astrocytes per image in the ONC group was significantly lower than in the healthy control group (7.13±1.5 and 10.47±1.9, respectively). Loss of astrocytes in the memantine-treated group was significantly lower (8.83±2.2) than in the ONC group. Assessment of inter-observer reliability showed excellent agreement among observations in control, ONC, and memantine groups. CONCLUSIONS The ONC is an effective method for investigation of astrocytic changes in mouse retina. Intravitreally administered memantine shows a promising glioprotective effect on mouse retinal astrocytes by preserving astrocyte count after ONC.
authors.affiliation: Department of Ophthalmology, Lithuanian University of Health Sciences, Academy of Medicine, Kaunas, Lithuania.
authors.forename: Ruta
authors.initials: R
authors.lastname: Maciulaitiene
authors.affiliation: Department of Ophthalmology, Lithuanian University of Health Sciences, Academy of Medicine, Kaunas, Lithuania.
authors.forename: Giedre
authors.initials: G
authors.lastname: Pakuliene
authors.affiliation: Vision Research Center and Department of Ophthalmology, University of Missouri, School of Medicine, Kansas City, MO, USA.|K.|Experimentica Ltd., Kuopio, Finland.
authors.forename: Simon
authors.initials: S
authors.lastname: Kaja
authors.affiliation: Institute of Anatomy, Lithuanian University of Health Sciences, Academy of Medicine, Kaunas, Lithuania.
authors.forename: Dainius Haroldas
authors.initials: DH
authors.lastname: Pauza
authors.affiliation: Experimentica Ltd., Kuopio, Finland.|University of Tampere, Tampere, Finland.
authors.forename: Giedrius
authors.initials: G
authors.lastname: Kalesnykas
authors.affiliation: Department of Ophthalmology, Lithuanian University of Health Sciences, Academy of Medicine, Kaunas, Lithuania.
authors.forename: Ingrida
authors.initials: I
authors.lastname: Januleviciene
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D058449:Intravitreal Injections; D008559:Memantine / Q000008:administration & dosage* / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D009409:Nerve Crush; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects*; D015588:Observer Variation; D009900:Optic Nerve / Q000473:pathology*; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D008559:Memantine