Suppression of experimental autoimmune optic neuritis by the novel agent fingolimod

J Neuroophthalmol. 2013 Jun;33(2):143-8. doi: 10.1097/WNO.0b013e31828ea2fc.


Purpose: Fingolimod is an immunomodulating agent that has been approved for the treatment of multiple sclerosis. Fingolimod-phosphate is an antagonist of sphingosine-1-phosphate receptor and known to act by preventing infiltration of autoreactive lymphocytes into the central nervous system. In this study, we investigated whether fingolimod prevents experimental autoimmune optic neuritis (EAON).

Methods: EAON was induced by immunizing C57BL/6 mice with myelin oligodendrocyte glycoprotein-derived peptide 35-55 (MOG-p). After MOG-p immunization, fingolimod was administered intragastrically from day 1 (entire phase study) or from day 9 (effector phase study) until day 35. Visual acuity of the mice was measured using OptoMotry on days 7, 14, 21, 28, and 35 after immunization. On day 35 after immunization, the mice were killed and eyes and entire length of the optic nerves were submitted for histopathologic evaluation.

Results: In the positive control group, visual acuity decreased markedly from approximately day 14 after immunization, reaching a nadir on day 21. In the fingolimod-treated groups in both entire phase and effector phase studies, there was only minimal decline in visual acuity on day 14 after immunization, and mild deterioration on day 21, followed by recovery. Histopathologic study showed that fingolimod given throughout the entire phase or only from the effector phase suppressed murine EAON. Immunohistochemical study for neurofilament demonstrated no irregularity of the linear structure of the optic nerve in the fingolimod-treated mice compared with the positive control group.

Conclusion: Fingolimod ameliorated EAON even when started after optic neuritis had developed. Further study is warranted to examine whether these findings are applicable to human disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Fingolimod Hydrochloride
  • Freund's Adjuvant / toxicity
  • Immunosuppressive Agents / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Neuritis, Autoimmune, Experimental / diagnosis
  • Neuritis, Autoimmune, Experimental / drug therapy*
  • Neuritis, Autoimmune, Experimental / etiology
  • Neuritis, Autoimmune, Experimental / pathology
  • Optic Nerve / pathology
  • Peptide Fragments / immunology
  • Pertussis Toxin / toxicity
  • Propylene Glycols / therapeutic use*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / therapeutic use
  • Statistics, Nonparametric
  • Visual Acuity / drug effects


  • Immunosuppressive Agents
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Propylene Glycols
  • myelin oligodendrocyte glycoprotein (35-55)
  • Freund's Adjuvant
  • Pertussis Toxin
  • Fingolimod Hydrochloride
  • Sphingosine