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Abstract

Click to add/remove this article to your list of 'My Favorites' Activation of the Wnt Pathway in the Retina, a New Pathogenic Mechanism for Diabetic Retinopathy

Year: 2009

Abstract Number: 860-P

Authors: JIAN-XING MA, YANG HU, TI ZHOU, KEVIN ZHOU, ROBERT MOTT, MINGYUAN WU, MICHAEL BOULTON, TIMOTHY J. LYONS, GUOQUAN GAO, YING CHEN

Institutions: Oklahoma City, OK, Guangzhou, Guangdong, China, Gainesville, FL

Results: Wnt signaling is known to mediate multiple biological and pathological processes, including development, angiogenesisits and inflammation. However, the association of the Wnt pathway with diabetic retinopathy (DR) has not been established. Here we show that retinal levels and nuclear translocation of beta-catenin, a key effector in the canonical Wnt pathway, were increased in humans with DR and in the retinas of Akita mice, streptozotocin-induced diabetic rats and oxygen-induced retinopathy rats. Retinal levels of low-density lipoprotein receptor-related proteins 5 and 6, co-receptors of Wnts, were also elevated in these DR models. The high glucose-induced activation of β-catenin was attenuated by an antioxidant, suggesting that oxidative stress is the direct cause of the Wnt pathway activation in diabetes. DKK1, a specific inhibitor of the Wnt pathway, ameliorated retinal inflammation, vascular leakage and retinal neovascularization in the DR models. DKK1 also blocked the generation of reactive oxygen species induced by high glucose, suggesting that Wnt signaling contributes to the oxidative stress in diabetes. These observations indicate that the Wnt pathway activation induced by high glucose plays a pathogenic role in retinal inflammation and neovascularization in DR and represents a novel therapeutic target.