title: Spermidine Ameliorates Neurodegeneration in a Mouse Model of Normal Tension Glaucoma.
abstract: OBJECTIVE
  To assess the therapeutic potential of spermidine in mice with excitatory amino acid carrier 1 (EAAC1) deletion (EAAC1 knockout [KO] mice), a mouse model of normal tension glaucoma.
  
  
  METHODS
  Spermidine, at 30 mM in drinking water, was administered to EAAC1 KO mice from 5 to 12 weeks old. Optical coherence tomography, multifocal electroretinograms, and the measurement of intraocular pressure (IOP) were performed at 5, 8, and 12 weeks old. Histopathology analyses were carried out at 8 and 12 weeks old, and immunoblot and immunohistochemical analyses of 4-hydroxy-2-nonenal (4-HNE) in the retina were performed at 8 weeks old.
  
  
  RESULTS
  Spermidine ameliorated retinal degeneration and improved visual function in EAAC1 KO mice at both 8 and 12 weeks old, without affecting IOP. A significant increase of 4-HNE was observed in vehicle-treated EAAC1 KO mice, but spermidine treatment reduced this increase, suggesting that spermidine alleviated the severity of the glaucoma-like phenotype by acting as an antioxidant.
  
  
  CONCLUSIONS
  The results from this study suggest that oral spermidine administration could be a useful treatment for retinal degenerative disorders including glaucoma.
authors.affiliation: Visual Research Project Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan 2Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Noro
authors.affiliation: Visual Research Project Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Namekata
authors.affiliation: Visual Research Project Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Azuchi
authors.affiliation: Visual Research Project Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kimura
authors.affiliation: Visual Research Project Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Guo
authors.affiliation: Visual Research Project Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Harada
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuneoka
authors.affiliation: Visual Research Project Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Harada
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004596:Electroretinography; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics; D015151:Immunoblotting; D007150:Immunohistochemistry; D007429:Intraocular Pressure; D057066:Low Tension Glaucoma / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D012160:Retina / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D012162:Retinal Degeneration / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D013095:Spermidine / Q000008:administration & dosage / Q000627:therapeutic use*; D041623:Tomography, Optical Coherence
chemical_list: D050580:Excitatory Amino Acid Transporter 3; C493399:Slc1a1 protein, mouse; D013095:Spermidine