Lutein acts via multiple antioxidant pathways in the photo-stressed retina

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.

Taurine Depletion Causes ipRGC Loss and Increases Light-Induced Photoreceptor Degeneration

“…1 Previous studies have shown that b-alanine treatment administered in the drinking water at a concentration of 3% causes a decline in taurine plasma levels [34][35][36] and in tissues such as the hippocampus, posterior cortex, and retina, as well as in cellular taurine content 13,14,[37][38][39][40] and also that taurine depletion causes loss of retinal neurons 6,41-43 (see below). [50][51][52] Light is a risk factor for some retinal degenerations, [53][54][55][56] and it accelerates photoreceptor degeneration in some inherited retinal degenerations. 54,[57][58][59] In previous work, [18][19][20]50 we documented that light exposure causes rapid photoreceptor degeneration and, longterm, alterations in all the retinal layers and RGC loss.…”

Lutein protects human retinal pigment epithelial cells from oxidative stress‑induced cellular senescence

“…Cellular senescence is characterized as an inability to proliferate despite the presence of sufficient nutrients but where cell viability and metabolic activity are still maintained (8). It is also a process through which cells undergo phenotypic changes, including chromatin alterations, tumor suppression, and interruption of cell division (9). Senescence is triggered by extreme cellular stress and may act as a protective mechanism against malignant cell degeneration.…”

“…Senescence is triggered by extreme cellular stress and may act as a protective mechanism against malignant cell degeneration. Common triggers for the onset of senescence are telomere shortening and dysfunction, DNA damage, oxidative stress, chromatin perturbations, oncogene activity, and strong mitogenic signals (7,9). Thus, common traits of senescent cells are altered cell morphology, cell cycle arrest, DNA damage, tolerance to apoptosis, inflammatory protein secretion, activation of tumor-suppressing mechanisms, and changes in gene expression.…”

“…Markers of cellular senescence include senescence-associated β-galactosidase (SA-β-gal), cell cycle arrest mechanisms, cell proliferation deficiency, DNA damage, DNA damage response activity, and various immune-related genes and cell regulatory factors. SA-β-gal is a representative senescence biomarker, as SA-β-gal activity is induced if cellular senescence occurs (7,9).…”

Effect of bradykinin on TGF-β1-induced retinal pigment epithelial cell proliferation and extracellular matrix secretion

“…Human RPE (hRPE) cells are frequently used in in vitro studies to investigate RPE-related disesases, as well as specific clinical treatments for these diseases. Thus, the hRPE cell line ARPE-19 was used in our study [2, 5, 6]. …”