Efficacy of Ethanol Extract of Fructus lycii and Its Constituents Lutein/Zeaxanthin in Protecting Retinal Pigment Epithelium Cells against Oxidative Stress: In Vivo and In Vitro Models of Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a large role in the pathogenesis of AMD. The present study was to evaluate the effects of Fructus lycii ethanol extract on AMD in mice and to investigate whether combination of lutein and zeaxanthin, two carotenoid pigments in Fructus lycii, could protect human retinal pigment epithelial ARPE-19 cells treated with hydrogen peroxide (H2O2) in vitro. We found that severe sediment beneath retinal pigment epithelium and thickened Bruch membrane occurred in AMD mice. However, Fructus lycii ethanol extract improved the histopathologic changes and decreased the thickness of Bruch membrane. Furthermore, the gene and protein expression of cathepsin B and cystatin C was upregulated in AMD mice but was eliminated by Fructus lycii ethanol extract. Investigations in vitro showed that ARPE-19 cell proliferation was suppressed by H2O2. However, lutein/zeaxanthin not only stimulated cell proliferation but also abrogated the enhanced expression of MMP-2 and TIMP-1 in H2O2-treated ARPE-19 cells. These data collectively suggested that Fructus lycii ethanol extract and its active components lutein/zeaxanthin had protective effects on AMD in vivo and in vitro, providing novel insights into the beneficial role of Fructus lycii for AMD therapy. 1. Introduction Age-related macular degeneration (AMD) represents a progressive chronic disease of the central retina and is a leading cause of vision loss worldwide. The cause of AMD is complex, and many risk factors have been implicated including age, genetics, diet, and other environmental risk factors. Most of the visual loss occurs in the late stages of the disease due to one of two processes: neovascular AMD (wet AMD) and atrophic AMD (dry AMD) [1]. The recent few decades have witnessed advances in the treatment of wet AMD. Antiangiogenic agents targeting choroidal neovascularization such as pegaptanib, bevacizumab, and ranibizumab have shown a therapeutic promise for wet AMD [2–4]. Unfortunately, there is currently no proven treatment for dry AMD in the clinical context. Increasing understanding of the pathogenesis of AMD reveals that cathepsin B and cystatin C have important functions in the catabolism of outer membranous disc of visual cells. Cathepsin B is a thiol-dependent lysosomal proteinase that can degrade collagens, connective tissue proteins, and certain native enzymes [5]. Visual cells also secrete cystatin C, resulting in protection of the surface proteins from degradation. More recently, epidemiological evidence
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