Abstract
Autoimmune uveitis is an inflammatory disease of the eye and is one of the major causes of blindness worldwide. Experimental autoimmune uveoretinitis (EAU) constitutes an animal disease model of human endogenous uveitis. In our study, we investigated the immunomodulatory effect of dimethyl fumarate (DMF) using bovine retinal extract-induced uveitis in a Female Wistar rats. To evaluate the in vivo efficacy, Female Wistar rats were divided into seven experimental groups: control group (n = 5), consisting of non-immunized animals; Uveoretinitis (n = 5), and DMF/Uveoretinitis groups (n = 15), which received a subcutaneous injection of bovine retinal extract emulsified in complete Freund's adjuvant; MC group (n = 5), treated by daily intragastric administration of methylcellulose 0.08% in tap water; DMF group, consisting of control positive group, rats received daily oral gavage administration of 500μL of dimethyl fumarate at 100mg/Kg dissolved in 0.08% methylcellulose in tap water (n = 5). On day 14 post immunization, the rats were then euthanized and associated indications were investigated to evaluate the therapeutic efficacy. Nitric oxide (NO) and TNF-α were assessed in plasma. Meanwhile, eyes were collected for histological and immunohistochemical studies. The retinal expression of iNOS, CD68, CD20, CD25, CD4, and CD8 was examined. Interestingly, DMF enhanced a significant reduction of NO and TNF-α production in the treated group. This effect was strongly related to the histological structure of eyes improvement. In the same context, a significant decrease of iNOS, CD68, and CD20 expression and CD25 increase expression were reported in retinal tissue of DMF/Uveoretinitis group in comparison to the immunized group. Collectively, our results indicate that DMF treatment has a beneficial effect in experimental autoimmune uveoretinitis and could constitute a good candidate for monitoring an ocular inflammatory diseases.
Highlights
Uveitis is a general term used for the inflammation of the uveal tissue
We investigated the immunomodulatory effect of Dimethylfumarate (DMF) using bovine retinal extract-induced uveitis in a Female Wistar rats
We investigated the effect of DMF on Nitric oxide (NO) production in Experimental autoimmune uveoretinitis (EAU)
Summary
Uveitis is a general term used for the inflammation of the uveal tissue (iris, ciliary body, and choroid). It has been classified as anterior, intermediate and posterior or as panuveitis. Noninfectious uveitis is believed to be autoimmune or immune-mediated (Gery et al 2002). Patients with autoimmune uveitis frequently showed the presence of immune responses against retinal soluble antigen (AgS), interphotoreceptor retinoid-binding protein (IRBP), and recoverin (Bansal et al 2015). Over the past several decades, animal models of autoimmune uveitis have been developed (Bansal et al 2015; Agarwal and Caspi 2004)
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