Abstract
Reactive oxygen species (ROS) are produced by host phagocytes and play an important role in antimicrobial actions against various pathogens. Autoimmune uveitis causes blindness and severe visual impairment in humans at all ages worldwide. However, the role of ROS in autoimmune uveitis remains unclear. We used ROS-deficient (Ncf1−/−) mice to investigate the role of ROS in experimental autoimmune uveitis (EAU). Besides, we also used the antioxidant N-acetylcysteine (NAC) treatment to evaluate the effect of suppression of ROS on EAU in mice. The EAU disease scores of Ncf1−/− mice were significantly lower than those of wild-type mice. EAU induction increased the levels of cytokines (interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-12, IL-17, and tumor necrosis factor (TNF)-α) and chemokines (monocyte chemoattractant protein (MCP)-1) in the retinas of wild-type mice but not in those of Ncf1−/− mice. EAU induction enhanced the level of NF-κB activity in wild-type mice. However, the level of NF-κB activity in Ncf1−/− mice with EAU induction was low. Treatment with the antioxidant NAC also decreased the severity of EAU in mice with reduced levels of oxidative stress, inflammatory mediators, and NF-κB activation in the retina. We successfully revealed a novel role of ROS in the pathogenesis of EAU and suggest a potential antioxidant role for the treatment of autoimmune uveitis in the future.
Highlights
Uveitis is among the most important causes of blindness and severe visual impairment worldwide
We monitored the effect of experimental autoimmune uveitis (EAU) on the stimulation of oxidative stress by measuring malondialdehyde, which serves as a marker for oxidative stress and is produced upon lipid peroxidation [24]
As neutrophil cytosolic factor 1 (Ncf1) is an essential component of NOX2 that generates Reactive oxygen species (ROS) to promote oxidative stress [15,16], we measured malondialdehyde in immunized Ncf1−/− mice (n = 7), in which a point mutation occurs at the 22 position of exon 8 to result in the aberrant splicing of transcripts and undetectable protein expression [25]
Summary
Uveitis is among the most important causes of blindness and severe visual impairment worldwide. Posterior uveitis tends to damage photoreceptor cells and leads to permanent blindness. Uveitis is often associated with autoimmune or inflammatory disorders, such as Behcet’s disease, ankylosing spondylitis, sarcoidosis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis in patients [2]. The etiologic triggers are unknown and have been postulated to include antigenic mimicry by microorganisms in conjunction with a concomitant adjuvant effect, leading to the priming of effector T lymphocytes capable of recognizing ocular antigens [5]. Autoimmune uveitis is a sight-threatening inflammatory disorder that affects humans at all ages [1]. Due to the nonspecific nature and the dose-limiting side effects of these drugs, the results of current treatment for autoimmune-mediated uveitis remain unsatisfactory [6]. An improved understanding of uveitis pathogenesis is needed to develop effective treatments
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
