Retinoic acid receptor stimulation ameliorates experimental autoimmune optic neuritis

Abstract

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. 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. 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. 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.