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: Hiroshi Keino, Takayo Watanabe, Yasuhiko Sato, Koichi Shudo, Yasushi Kitaoka, Takayuki Harada, Annabelle A Okada
• Journal: Clinical & experimental ophthalmology (Clin Exp Ophthalmol) Vol. 43 Issue 6 Pg. 558-67 (Aug 2015) ISSN: 1442-9071 [Electronic] Australia
• PMID: 24612001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Chemical References

• Benzoates
• Interleukin-17
• Rara protein, mouse
• Receptors, Retinoic Acid
• Retinoic Acid Receptor alpha
• Tetrahydronaphthalenes
• retinoic acid receptor beta
• tamibarotene
• Tretinoin
• Interferon-gamma
• Sod1 protein, mouse
• Superoxide Dismutase
• Superoxide Dismutase-1

Topics

• Animals
• Benzoates (therapeutic use)
• Encephalomyelitis, Autoimmune, Experimental (metabolism, prevention & control)
• Female
• Flow Cytometry
• Injections, Intraperitoneal
• Interferon-gamma (metabolism)
• Interleukin-17 (metabolism)
• Mice
• Mice, Inbred C57BL
• Neuritis, Autoimmune, Experimental (metabolism, prevention & control)
• Oligonucleotide Array Sequence Analysis
• Optic Neuritis (metabolism, prevention & control)
• Receptors, Retinoic Acid (agonists, metabolism)
• Retinoic Acid Receptor alpha
• Superoxide Dismutase (metabolism)
• Superoxide Dismutase-1
• Tetrahydronaphthalenes (therapeutic use)
• Tretinoin (therapeutic use)