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Takeshi Kezuka, Yoshihiko Usui, Gyomei An, Yoshimichi Matsunaga, Ryusaku Matsuda, Akihiko Umazume, Naoyuki Yamakawa, Hiroshi Goto; Suppression of Experimental Autoimmune Optic Neuritis By The Novel Agent FTY720. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2982.
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© ARVO (1962-2015); The Authors (2016-present)
FTY720 (IMUSERA®) is an immunnomodulatory agent that has been approved as a new therapeutic drug for multiple sclerosis. FTY720 is known to act by preventing infiltration of autoreactive lymphocytes into the central nervous system, as S1P receptor functional antagonist. In this study, we investigated whether FTY720 prevents experimental autoimmune optic neuritis (EAON).
EAON was induced by immunizing C57BL/6 mice subcutaneously on the back with myelin oligodendrocyte glycoprotein derived peptide 35-55 (MOG-p). At the same time, the mice were injected Bordetella pertussis toxin 1 µg/mouse intraperitoneally as an additional adjuvant. After MOG-p immunization, FTY720 at 0.3 mg/kg that is the dose used in human treatment was administered intragastrically using a probe. Positive control mice were prepared by administering distilled water to MOG-p-immunized mice. Visual acuity of the mice was measured using OptoMotry® (CerebralMechanics Inc.) on days 7, 14, 21, 28 and 35 after immunization. On day 34 after immunization, mice received an intradermal injection of MOG-p suspended in PBS into the ear pinnae. After 24 hours, ear swelling was measured by a micrometer. On day 35 after immunization, the mice were sacrificed, and eyeballs were extracted until the optic chiasm for histopathological evaluation of EAON.
In the positive control group, visual acuity decreased gradually after immunization from around day 14 after immunization, and visual acuity wasmost decreased on day 21. On the other hand, in the FTY720 administered group, there was only minimal decline in visual acuity even after day 14 of immunization, and deterioration of visual acuity was mild on day 21. Delayed type hypersensitivity reaction tended to be diminished in the FTY720 administered group, but there was no significant difference from the control group. FTY720 dosing resulted in dramatic amelioration in histopathological disease severity of EAON.
The new agent FTY720 ameliorated experimental autoimmune optic neuritis, and has the potential to become the first oral agent for specific treatment of human optic neuritis.
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