title: The Relationship Between the Renin-Angiotensin-Aldosterone System and NMDA Receptor-Mediated Signal and the Prevention of Retinal Ganglion Cell Death.
abstract: Excitotoxicity, which is due to glutamate-induced toxic effects on the retinal ganglion cell (RGC), is one of several mechanisms of RGC loss. The renin-angiotensin-aldosterone system (RAAS) has also been implicated in RGC death. Therefore, it is important to determine the exact relationship between the RAAS and N-methyl-d-aspartate (NMDA) receptor-mediated signal in order to prevent RGC death.
  
  
  
  N-methyl-d-aspartate or aldosterone was injected into the vitreous body. After intravitreal injection of NMDA or aldosterone, animals were treated with spironolactone or memantine. Retinal damage was evaluated by measuring the number of RGCs at 4 weeks after local administration of aldosterone or at 2 weeks after local administration of NMDA. Vitreous humor levels of aldosterone were measured using enzyme immunoassay kits.
  
  
  
  A significantly decreased number of RGCs were observed after intravitreal injection of NMDA. Although spironolactone did not show any neuroprotective effects, memantine significantly reduced NMDA-induced degeneration in the retina. Furthermore, a significant decrease in the number of RGCs was observed after an intravitreal injection of aldosterone. While memantine did not exhibit any neuroprotective effects, spironolactone caused a significant reduction in the aldosterone-induced degeneration in the retina. There was no change in the aldosterone concentration in the vitreous humor after an NMDA injection.
  
  
  
  Our findings indirectly show that there is no relationship between the RAAS and NMDA receptor-mediated signal with regard to RGC death.
authors.affiliation: Department of Ophthalmology, Kagawa University, Faculty of Medicine, Kagawa, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Ophthalmology, Kagawa University, Faculty of Medicine, Kagawa, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hirooka
authors.affiliation: Department of Ophthalmology, Kagawa University, Faculty of Medicine, Kagawa, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Ono
authors.affiliation: Department of Ophthalmology, Kagawa University, Faculty of Medicine, Kagawa, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Department of Pharmacology, Kagawa University, Faculty of Medicine, Kagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.affiliation: Department of Ophthalmology, Kagawa University, Faculty of Medicine, Kagawa, Japan.
authors.forename: Akitaka
authors.initials: A
authors.lastname: Tsujikawa
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002452:Cell Count; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage; D058449:Intravitreal Injections; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*; D012164:Retinal Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014822:Vitreous Body / Q000378:metabolism / Q000473:pathology
chemical_list: D018690:Excitatory Amino Acid Agonists; D016194:Receptors, N-Methyl-D-Aspartate; D000450:Aldosterone; D016202:N-Methylaspartate