Resveratrol reverses the effect of TNF-α on inflammatory markers in a model of autoimmune uveitis

Introduction: Uveitis is an disorder that causes intraocular inflammation resulting in retinal damage which eventually leads to blindness. Current treatment involves prolonged use of corticosteroids which, due to the progressive nature of the disease, leads to adverse side effects such as increased intraocular pressure, retinal tears or detachment, and adverse systemic symptoms associated with steroid use. Resveratrol is a natural polyphenol found in many plants and other organic sources. In humans it effectively protects against oxidative damage, aids in vascular support and immune regulation, and down-regulates inflammatory cytokines. This study sought to demonstrate potential benefits of resveratrol in reversing the inflammatory response in a model of autoimmune uveitis (AU). Methods: Pigmented retinal epithelial cells were treated with TNF-alpha to induce an inflammatory response. Cells were then exposed to resveratrol at 50 M, 100 M and 200 M for 12, 24, and 48 h both pre- and post- TNF-treatment. Inflammatory response was assessed by qPCR arrays containing inflammatory cytokines and receptors. Five genes were selected for qPCR validation based on the magnitude of the observed effect and their relevance to uveitis pathology: IL-33, IL-17F, FASL, VEGFA, and Chemokine ligand 2. Results: Resveratrol significantly reversed the effect of TNF-alpha on each target in either a time- or dose-dependent manner. Resveratrol pretreatment attenuated this effect when cells were subsequently treated with TNF-alpha. Conclusions: Resveratrol has potential both as a non-invasive treatment and as a preventive for autoimmune uveitis in humans, while avoiding the negative side effects of corticosteroid therapies.