title: Functional protective effects of long-term memantine treatment in the DBA/2J mouse.
abstract: OBJECTIVE
  To analyse the effects of long-term memantine treatment on the retinal physiology and morphology of DBA/2J mice.
  
  
  METHODS
  DBA/2J (D2J) mice received i.p. injections of the NMDA receptor antagonist memantine, which protects neurons from abnormally elevated glutamate levels, twice a day over a period of 7 months. At the age of 2, 6 and 10 months, the intraocular pressure (IOP) and electroretinograms (ERGs) were measured in all treated D2J mice, in untreated D2J controls and in C57Bl/6 (B6) wild-type mice. After the last measurement at the age of 10 months, the mice were killed and the retinae and the optic nerves were analysed morphologically.
  
  
  RESULTS
  The IOP increased with age in both D2J and B6 mice with a larger increase in the D2J strain. IOPs were not influenced by memantine treatment. The response amplitude of the scotopic flash ERG decreased with age in the D2J strain. This amplitude decrease, particularly that of the b-wave, was smaller in treated D2J mice. The retinae of treated D2J mice exhibited less peripheral degeneration of cone photoreceptors, and optic nerve neuropathy was less frequent.
  
  
  CONCLUSIONS
  Application of the NMDA receptor antagonist memantine diminished retinal neurodegeneration in the D2J mice and had a protective effect on the b-wave amplitude of the scotopic flash ERG. This protection may occur secondarily as memantine primarily acts on retinal ganglion cells.
authors.affiliation: Department of Ophthalmology, University Hospital Erlangen, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Atorf
authors.forename: Michael
authors.initials: M
authors.lastname: Scholz
authors.forename: Fabian
authors.initials: F
authors.lastname: Garreis
authors.forename: Julia
authors.initials: J
authors.lastname: Lehmann
authors.forename: Lars
authors.initials: L
authors.lastname: Bräuer
authors.forename: Jan
authors.initials: J
authors.lastname: Kremers
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D004596:Electroretinography / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D015812:Glaucoma, Angle-Closure / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007429:Intraocular Pressure / Q000187:drug effects*; D008559:Memantine / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D018613:Microscopy, Confocal; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015259:Dopamine Agents; D008559:Memantine