title: Retinoic acid receptor stimulation ameliorates experimental autoimmune optic neuritis.
abstract: BACKGROUND
  To determine whether all-trans retinoic acid or a synthetic retinoic acid receptor-α/β-specific agonist, Am80, can reduce the degree of experimental autoimmune optic neuritis in mice with experimental autoimmune encephalomyelitis.
  
  
  METHODS
  Optic neuritis was induced in C57BL/6 mice by immunizing them with myelin oligodendrocyte glycoprotein35-55 . All-trans retinoic acid (350 μg/mouse/time point) or Am80 (5 mg/kg/time point) was administered every other day from day 0 to day 20. The degree of experimental autoimmune encephalomyelitis was scored and histopathological analysis of the optic neuritis was performed on day 22 after the immunization. In vivo-primed draining lymph node cells obtained from vehicle-treated or all-trans retinoic acid-treated mice were stimulated with myelin oligodendrocyte glycoprotein35-55 , and the culture supernatant was collected for assays of interferon-γ and interleukin-17.
  
  
  RESULTS
  All-trans retinoic acid treatment significantly reduced the clinical score of experimental autoimmune encephalomyelitis and the severity of the optic neuritis by histopathological analysis. The production of interferon-γ and interleukin-17 was significantly reduced in all-trans retinoic acid-treated mice compared with vehicle-treated mice. Am80 treatment also significantly decreased the severity of the optic neuritis in mice with experimental autoimmune encephalomyelitis.
  
  
  CONCLUSIONS
  These findings demonstrate that all-trans retinoic acid and Am80 treatment were able to reduce the severity of optic neuritis in mice with experimental autoimmune encephalomyelitis. Activation of retinoic acid receptor-α/β may be a molecular target for the treatment of autoimmune optic neuritis induced by Th1 or Th17-dominated immune responses.
authors.affiliation: Department of Ophthalmology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Keino
authors.affiliation: Department of Ophthalmology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Takayo
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Division of Radioisotope Research, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: The Research Foundation ITSUU Laboratory, Setagaya-ku, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Shudo
authors.affiliation: Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kitaoka
authors.affiliation: Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Ophthalmology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Annabelle A
authors.initials: AA
authors.lastname: Okada
mesh_terms: D000818:Animals; D001565:Benzoates / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009444:Neuritis, Autoimmune, Experimental / Q000378:metabolism / Q000517:prevention & control*; D020411:Oligonucleotide Array Sequence Analysis; D009902:Optic Neuritis / Q000378:metabolism / Q000517:prevention & control*; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D014212:Tretinoin / Q000627:therapeutic use
chemical_list: D001565:Benzoates; D020381:Interleukin-17; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D013764:Tetrahydronaphthalenes; C082925:retinoic acid receptor beta; C061133:tamibarotene; D014212:Tretinoin; D007371:Interferon-gamma; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Th1; Th17; experimental autoimmune optic neuritis; retinoid