The Effect Of Intravitreal Methotrexate In A Rabbit Model Of Experimentally Induced Uveitis

Abstract

Abstract: : Purpose:To study the effect of intravitreally administered methotrexate (MTX) in experimentally induced uveitis in a rabbit model. Materials and Methods:Uveitis was induced in 18 rabbits by injecting retinal s–antigen (RSA) in complete Freund's adjuvant subconjunctivally in the right eye. Methotrexate (400 µg in 50 µl) was administered intravitreally to the right eyes of 9 rabbits (MTX group) on the 21^th day after the retinal s–antigen injection and continued three times a week for 18 days. Balanced salt solution (BSS) (50 µl) was administered in a similar fashion to 9 rabbits (Control group). Inflammation was graded based on number and size of chorioretinal lesions. On 39^th day after RSA injection, the rabbits were sacrificed and eyes were enucleated for histopathologic examination. The differences in severity and progression of inflammation of the right eyes in the 2 groups were compared. Results:In the MTX group, on the 39^th day, 5 rabbits (55.7%) did not have any clinically detectable uveitis;one of these had uveitis on day 32 which resolved by day 35. The other 4 rabbits (44.3%) had only mild to moderate uveitis. In contrast, 8 control rabbits (88.8%) developed clinically detectable posterior uveitis, and 37.5% of them had a severe form. Only 1 rabbit in this group (11.2%) did not develop uveitis. Uveitis in the control group occurred earlier, and was more severe than in the MTX group as depicted in Figure 1. The difference in severity of inflammation between the 2 groups reached statistical significance on day 25 (P < 0.04) and day 39 (P < 0.018). Histopathology confirmed these findings, and did not reveal any retinal toxicity secondary to methotrexate. Conclusions:Intravitreal methotrexate was effective in reducing or preventing intraocular inflammation compared with placebo in an animal model of uveitis. No toxicity was observed. Intravitreal methotrexate may be a potential addition to our armamentarium for the treatment of non–infectious uveitis.  

Keywords: uveitis–clinical/animal model • chorioretinitis • immunomodulation/immunoregulation