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. 2016 Jul 22;6:30226.
doi: 10.1038/srep30226.

Lutein Acts via Multiple Antioxidant Pathways in the Photo-Stressed Retina

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Free PMC article

Lutein Acts via Multiple Antioxidant Pathways in the Photo-Stressed Retina

Mamoru Kamoshita et al. Sci Rep. .
Free PMC article

Abstract

Lutein slows the progression of age-related macular degeneration (AMD), a leading cause of blindness in ageing societies. However, the underlying mechanisms remain elusive. Here, we evaluated lutein's effects on light-induced AMD-related pathological events. Balb/c mice exposed to light (2000 lux, 3 h) showed tight junction disruption in the retinal pigment epithelium (RPE) at 12 h, as detected by zona occludens-1 immunostaining. Substantial disruption remained 48 h after light exposure in the vehicle-treated group; however, this was ameliorated in the mice treated with intraperitoneal lutein at 12 h, suggesting that lutein promoted tight junction repair. In the photo-stressed RPE and the neighbouring choroid tissue, lutein suppressed reactive oxygen species and increased superoxide dismutase (SOD) activity at 24 h, and produced sustained increases in sod1 and sod2 mRNA levels at 48 h. SOD activity was induced by lutein in an RPE cell line, ARPE19. We also found that lutein suppressed upregulation of macrophage-related markers, f4/80 and mcp-1, in the RPE-choroid tissue at 18 h. In ARPE19, lutein reduced mcp-1 mRNA levels. These findings indicated that lutein promoted tight junction repair and suppressed inflammation in photo-stressed mice, reducing local oxidative stress by direct scavenging and most likely by induction of endogenous antioxidant enzymes.

Figures

Figure 1
Figure 1. Repair of photo-induced tight junction disruption was promoted by lutein.
Whole mount RPE immunostaining for ZO-1 and counterstaining using Hoechst. (a) Light exposure disrupted the ZO-1 (green) staining pattern in the RPE at both 12 and 24 h; this disruption was reduced at 7 days. Hoechst (blue) showed no obvious change during this time-course. (b) At 48 h, the disruption of the ZO-1 pattern was attenuated by lutein treatment at 12 h, as compared with vehicle treatment. (c) The number of RPE cells with an intact ZO-1 pattern at all edges of the RPE cells per total RPE cells were shown in a graph. RPE, retinal pigment epithelium; n = 6; **p < 0.01. Scale bar, 100 μm.
Figure 2
Figure 2. ROS levels were suppressed by lutein in the photo-stressed RPE-choroid.
ROS levels, as indicated by DCFH-DA fluorescent intensity, were attenuated by lutein treatment 24 h after light exposure in the photo-stressed RPE-choroid. RPE, retinal pigment epithelium; n = 6; **p < 0.01.
Figure 3
Figure 3. Lutein induced SOD activity and mRNA expression in the photo-stressed RPE-choroid.
(a) Light exposure induced SOD activity in the RPE-choroid 24 h after light exposure; this induction was greater in lutein-treated mice. (b) Levels of sod1 and sod2 mRNAs, as determined by real-time RT-PCR. RPE, retinal pigment epithelium; n = 6; *p < 0.05, **p < 0.01.
Figure 4
Figure 4. Lutein induced SOD activity in the ARPE19 cell line.
SOD activity is shown in the ARPE19 cell line 3 h after exposure to the indicated concentrations of lutein; n = 4; *p < 0.05, **p < 0.01.
Figure 5
Figure 5. Lutein suppressed macrophage recruitment in the photo-stressed RPE-choroid.
Photo-stress induced f4/80 (a) and mcp-1 (b) mRNAs, as determined by real time RT-PCR, at 18 h; lutein treatment suppressed this induction. RPE, retinal pigment epithelium; n = 6; *p < 0.05, **p < 0.01.
Figure 6
Figure 6. Lutein suppressed mcp-1 mRNA in the ARPE19 cell line.
Lutein reduced mcp-1 mRNA levels in the ARPE19 cell line, as determined by real-time RT-PCR, in a concentration-dependent manner 3 h after addition of the indicated concentrations of lutein to the culture medium; n = 6; *p < 0.05, **p < 0.01.

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