Fingolimod (FTY720) as an acute rescue therapy for intraocular inflammatory disease.
OBJECTIVE
To examine the efficacy of the immunomodulatory drug fingolimod (FTY720) as a rescue therapy for noninfectious intraocular inflammation.


METHODS
Experimental autoimmune uveoretinitis, the murine correlate of human uveitis, was induced in B10.RIII mice. The mice were treated with 2 oral doses of fingolimod daily, either during early ocular infiltration or following clinical onset of the disease. At subsequent times, retinal infiltrates were examined and enumerated using flow cytometry, and structural disease was assessed and scored using histology.


RESULTS
Fingolimod treatment, administered 2 days before disease onset, prevented inflammatory cells from infiltrating the retina, with corroborative suppression of histologic disease. A single dose of fingolimod was sufficient in clearing infiltrating leukocytes from the retina within 2 hours of treatment. Furthermore, a single dose of fingolimod administered after disease onset not only abolished retinal infiltrates but also prevented disease relapse for at least 3 weeks.


CONCLUSIONS
A short-term, high-dose treatment with fingolimod rapidly reduces ocular infiltrates in experimental autoimmune uveoretinitis, leading to a normal myeloid cell count within the retina. When given at the early stages of intraocular inflammation, fingolimod resolves disease. Clinical Relevance This study directly demonstrates the therapeutic potential of fingolimod and an acute rescue intervention for human noninfectious posterior-segment intraocular inflammatory disease.
Raveney
Ben J E
BJ
Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. ben@raveney.co.uk
Copland
David A
DA
Nicholson
Lindsay B
LB
Dick
Andrew D
AD
D000284:Administration, Oral; D000818:Animals; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004638:Emergency Treatment / Q000379:methods; D005260:Female; D000068876:Fingolimod Hydrochloride; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D011409:Propylene Glycols / Q000008:administration & dosage*; D011897:Random Allocation; D012016:Reference Values; D012173:Retinitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012680:Sensitivity and Specificity; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine