TRANS-RESVERATROL AS TREATMENT FOR EQUINE RECURRENT UVEITIS

Uveitis is the leading cause of vision loss in the equine population with an incidence rate between 10-12%. Uveitis is an auto immune disorder that causes the retinal cells to be attacked and eventually leads to blindness. Current treatment involves the prolonged use of the glucocorticosteroid dexamethasone which, due to the ongoing nature of the disease, leads to detrimental side effects. These include, but are not limited to, drastic change in behavior, liver disease and laminitis. Resveratrol (trans-3,4’,5,-trihydroxystilbene) is a naturally occurring polyphenol molecule found in many plant species including grapes, peanuts, cranberries, Japanese giant knotweed and others. In these plants resveratrol acts as an antioxidant to protect the plant from bacteria, fungi and ultraviolet radiation. When used in human studies, both in vitro and in vivo, resveratrol was found to protect against oxidative damage and premature aging, aid in vascular support and immune regulation, blocked the carcinogen effects of TNF-α and NF-κB, and down regulated inflammatory cytokines. In this study human ARPE cell lines were cultured and then treated separately with TNF-α to induce an inflammatory response. From there each cell treatment received resveratrol at 50, 100 and 200µm for 12, 24, and 48 hours. Three controls, non-treated cells, resveratrol treated cells and TNF-α only treated cells, were also included in the experiments. The RNA extracted from these experiments was then reverse transcribed to cDNA and run on a qPCR array that contained eighty-four inflammatory cytokines and receptors. Five genes were selected for validation of their effect on ERU and the remaining data retrieved for further study. In all five genes selected, Interleukin 33, Interleukin 17F, Fas Ligand, Vascular endothelial growth factor A, and Chemokine ligand 2, resveratrol was shown to have a significant effect on gene expression either in a time, dose or time/dose dependent manner. Pretreatment with resveratrol yielded an attenuation of the expression of several genes after TNF-α treatment. These results show that resveratrol is a viable option for the treatment of equine recurrent uveitis.