Treatment of autoimmune retinopathies with anti-aging polyphenol resveratrol

Oregon Health & Science University, Portland OR

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Retinal degeneration is one of the leading causes of vision loss and blindness in the world. Some retinopathies are caused by autoimmune processes. Autoantibodies against retinal proteins are strongly associated with retinal degeneration in patients with autoimmune and paraneoplastic retinopathies. In these retinopathies, antibody-triggered apoptotic death of retinal cells progressively causes significant tissue damage, loss of vision, and blindness. Age is the strongest risk factor for the incidence of retinopathies in adult Americans. Our studies show that the average age of patients with cancer-associated retinopathy (CAR) or autoimmune retinopathy (AR) is about 62 years. Currently, there is no approved therapy for treating these patients and the corticosteroid and immunomodulation therapies that are frequently offered are ineffective. Moreover, anti-aging mechanisms have not been factored into designing therapeutics for visual loss. We propose a novel non-steroidal protection treatment using the anti-aging drug resveratrol (RES), a polyphenolic phytoalexin found in purple grapes, for treating autoimmune retinopathies. We hypothesize that RES induces anti-apoptotic mechanisms that confer neuroprotection against antibody-induced cell death in the retinas of patients with CAR and AR. The long-term goal of this study is to identify safe and effective therapeutic compounds like RES for treatment of autoimmune diseases of the eye and to define their protective mechanisms at the molecular level. The main objectives of this study are to define a mechanism by which RES prevents the expression of apoptotic proteins in the rat retina, induces anti-aging SIRT1 protein expression, and how aging influences the expression of SIRT1 in a rat model for CAR. To achieve these objectives, the following specific aims are proposed: (Aim 1) To determine the therapeutic effects of RES against antibody-induced retinal cell death in Sprague-Dawley (SD) rats, and (Aim 2) To determine the effects of retinal aging on antibody-induced retinopathy and define the mechanism of RES protection using young and old SD rats.