Efficacy of Ethanol Extract ofFructus lyciiand Its Constituents Lutein/Zeaxanthin in Protecting Retinal Pigment Epithelium Cells against Oxidative Stress:In VivoandIn VitroModels of Age-Related Macular Degeneration

Abstract

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.

The Pharmacological Effects of Lutein and Zeaxanthin on Visual Disorders and Cognition Diseases

“…Cathepsin B is a thiol-dependent lysosomal proteinase that can degrade collagens, connective tissue proteins, and certain native enzymes [ 58 ]. Furthermore, the expression of cathepsin B and cystatin C was significantly increased at both gene and protein levels in mice with an experimental model of AMD, which further strengthened the association of these two enzymes with the development of AMD [ 59 ]. Visual cells also secrete cystatin C, resulting in protection of the surface proteins from degradation.…”

“…In the pathogenesis of AMD, the equilibrium between MMP-2 and TIMP-2 is disrupted, promoting the progression of the disease [ 75 ]. Present data [ 59 ] showed that these two molecules were all upregulated in ARPE-19 cells under oxidative stress. However, L/Z abolished the elevated expression of MMP-2 and TIMP-2 in H 2 O 2 -treated ARPE-19 cells, suggesting that L/Z could be beneficial for oxidative stress-involved AMD by regulating matrix homeostasis.…”

Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration

“…Many factors contribute to AMD. One dominant factor is the increasing age of the retina, where the RPE becomes damaged due to a progressively impaired DNA repair system that fails to repair oxidative damage from prolonged exposure to visible light, ultraviolet A and reactive oxygen species (ROS) over time 2 . Cigarette smoking is another factor that contributes to the production of ROS and oxidative damage on the RPE layer.…”

Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration

“…I cannot judge that effects of LSF result from protection against H2O2-induced cell death or an increased proliferation. 24 h treatment with H2O2 has been shown to cause toxicity in ARPE-19 cells 1 2 . The underlying raw data also demonstrate that the absorbance was reduced from 2.0+ to 1.0+ between CA-H2O2 (fig.1A) and CA+H2O2 (Fig.1b), if comparable.…”