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Mycophenolate mofetil and cyclophosphamide treatments suppress inflammation intensity in an experimental model of autoimmune uveitis

Klmov, A;Seidler tanogov, P;Heissigerov, J;Svozlkov, P;Kuera, T;

In human, autoimmune uveitis is a leading cause of visual disability and ranks with diabetic retinopathy as a major source of blind registrations in developed countries. Since most cases of non-infectious uveitis are considered to be autoimmune or at least immune-mediated, the management of such patients has rested on appropriate immunosuppression. Some patients, however, despite maximal immunotherapy, fail to respond or are seriously intolerant of the drug therapies. Since its establishment 20 years ago, the model of experimental autoimmune uveoretinitis has served as a useful template for novel therapeutic approaches. The aim of our study was to compare the efficacy of mycophenolate mofetil and cyclophosphamide and golimumab treatment in the mouse model of experimental autoimmune uveitis. The intensity of intraocular inflammation was evaluated histologically in the treatment and control groups. Experimental autoimmune uveitis has been induced in mouse strain C57BL/6 by subcutaneous application of interphotoreceptor retinoid binding protein in complete Freund's adjuvant and pertussis toxin. The treatment was commenced on the day of uveitis induction. Cyclophosphamide was applied intraperitoneally in a single dose (100 mg/kg), mycophenolate mofetil intraperitoneally daily (30 mg/kg or 50 mg/kg), golimumab subcutaneously weekly (70 mg/kg). Sham intraperitoneal injection of a placebo (aqua pro injectione) and untreated mice with experimental autoimmune uveitis served as controls. The results show statistically significant suppression of experimental uveitis both with mycophenolate mofetil and with cyclophosphamide, and thus support its use in human medicine.