Abstract
Angiogenin (ANG) is involved in the innate immune system and inflammatory disease. The aim of this study is to evaluate the anti-inflammatory effects of ANG in an endotoxin induced uveitis (EIU) rat model and the pathways involved. EIU rats were treated with balanced salt solution (BSS), a non-functional mutant ANG (mANG), or wild-type ANG (ANG). The integrity of the blood-aqueous barrier was evaluated by the infiltrating cell and protein concentrations in aqueous humor. Histopathology, Western blot, and real-time qRT-PCR of aqueous humor and ocular tissue were performed to analyze inflammatory cytokines and transcription factors. EIU treated with ANG had decreased inflammatory cells and protein concentrations in the anterior chamber. Compared to BSS and mANG, ANG treatment showed reduced expression of IL-1β, IL-8, TNF-α, and Myd88, while the expression of IL-4 and IL-10 was increased. Western blot of ANG treatment showed decreased expression of IL-6, inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and phosphorylated NF-κB and increased expression of IL-10. In conclusion, ANG seems to reduce effectively immune mediated inflammation in the EIU rat model by reducing the expression of proinflammatory cytokines, while increasing the expression of anti-inflammatory cytokines through pathways related to NF-κB. Therefore, ANG shows potential for effectively suppressing immune-inflammatory responses in vivo.
Highlights
Ocular inflammation is one of the main causes of blindness and visual disturbance [1,2]
We focused on the contribution of the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88) pathway for activation of nuclear factor-κB (NF-κB)
Treatment with mutant ANG (mANG) had little or no effect in decreasing inflammation, while ANG treatment showed a substantial decrease in cells and fibrinous membrane in the anterior chamber
Summary
Ocular inflammation is one of the main causes of blindness and visual disturbance [1,2]. Uveitis is a sight threatening disease that results from acute, recurrent, or chronic inflammation of the uvea [1] and is involved with the immune system [3,4]. Chronic recurrence can be detrimental and cause irreversible visual impairment and blindness. It accounts for 10–15% of all blindness worldwide [5,6,7]. The aim of treatment for chronic uveitis is long term control of inflammation. The current mainstay treatment for uveitis is topical or systemic steroids, but their long term use may have serious ocular and systemic side effects [4,23].
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