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

Abstract

Oxidative stress-induced cellular senescence is an important contributor to the pathogenesis of age-related macular degeneration (AMD). Characteristics of premature cellular senescence include a loss of proliferation, change in cell shape, irreversible cell cycle arrest, and elevated senescence-associated β-galactosidase (SA-β-gal) activity. It was hypothesized that lutein may have anti-senescence potential and may be useful as a treatment for AMD. In the present study, premature cellular senescence was induced in ARPE-19 cells via treatment with H 2 O 2 and the effects of lutein application were confirmed by observing cell morphology, lysosome contents, reactive oxygen species (ROS) generation and SA-β-gal activity, and cell cycle progression. The protein expression was also analyzed via western blotting in order to identify the affected signaling pathways. The results revealed that H 2 O 2 treatment induced premature cellular senescence in ARPE-19 cells, as evidenced by an increased production of ROS and SA-β-gal, altered lysosome contents, changed cellular morphology and arrested cell cycle progression. However, when treated with lutein, ARPE-19 cells were effectively protected from these H 2 O 2 -induced effects. Western blot analysis revealed that lutein induced the expression of heme oxygenase-1, NAD(P)H quinone dehydrogenase 1, sirtuin (SIRT)-1, and SIRT3. Together, the results indicated that lutein protects cells from cellular senescence induced by oxidative stress; therefore, it may be able to suppress the progression of AMD. In addition, our increased understanding of the pathways through which lutein acts is useful for the development of novel therapies for the treatment of oxidative stress-associated retinal disease.Abbreviations: WST-1, water-soluble tetrazolium salt-1;CM-H 2 DCFDA, chloromethyl derivative of 2' ,7'-dichlorodihydrofluorescein diacetate; ROS, reactive oxygen species; SA-β-gal, senescence-associated β-galatosidase; PI, Propidium iodide; HO-1, heme oxygenase-1; NQO1, NAD(P)H quinone dehydrogenase 1; Nrf2, nuclear factor erythroid 2-related factor 2; SIRT1, sirtuin-1; SIRT3, sirtuin-3

Effects of lutein supplementation in age-related macular degeneration

“…Culture, animal and human studies have shown that retinal concentrations of lutein are inversely related to the risk of AMD [42, 45, 48]. The same study also provided evidence that low concentration of lutein may actually cause AMD [48].…”

“…Lutein and other carotenoids also suppress production of inflammatory mediators and reactive oxygen species, and they down-regulate NADPH oxidase subunit Nox4 [43, 44]. In cell culture studies, lutein protected ARPE-19 retinal cells from oxidative stress-induced cellular senescence [45], likely by quenching singlet oxygen [46]. These anti-oxidative properties have led to the suggestion that lutein may slow AMD progression and alleviate symptoms [47].…”

Chitosan-sodium alginate-fatty acid nanocarrier composite: lutein bioavailability, absorption pharmacokinetics in diabetic rat and protection of retinal cells against H2O2 induced oxidative stress in vitro

“…Other possible reasons for ROS lowering effect could be the slow and sustainable release of lutein from natural polymers CS and SA (S.-S. Feng, 2004;Niamprem et al, 2014). Chae, Park, and Park (2018) also reported that lutein (10 µM) treatment prior to H2O2 (100 µM for 2h), decreased the ROS levels (26.03%) in ARPE-19 cells. However, lutein delivered in NCs developed in the current study e ciently brought back the intracellular ROS to the normal level.…”

“…Characteristics of SA (viscosity 175 cP) was measured at 1% SA (w/v) in the water at 25 °C, 100 rpm and 17.5% torque using the spindle number 1 (Brook eld viscometer, RV DV-II+Pro, USA), FTIR spectroscopy (Bruker, Tensor II, Germany) was used quantify the mannuronate/guluronate (M/G) ratio (1.84) of SA (Chandıa, Matsuhiro, & Vásquez, 2001;Dodero, Vicini, Alloisio, & Castellano, 2019;Filippov & Kohn, 1974) in particular, correlating absorption band at 808 cm-1 assigned to M units and 787 cm-1 to G units. The interaction of chitosan-sodium alginate polymer composite is given in Figure 1.…”

A Simple Route to the Complexation of Lutein with Reduced Graphene Oxide Nanocarriers and Antioxidant Protection Against Blue Light

“…Numerous biological processes within cells are regulated by ROS, including inflammation, apoptosis, and senescence, and it is known that ROS at basal levels are important for cell proliferation. 23 However, at high concentrations of ROS can be toxic to cells, 24 and then the promotion of DNA damage and cellular senescence, implicates in the development of a variety of diseases, including cancer and diabetes. Therefore, one of the key considerations for maintaining the homeostasis of the living body and for protecting against oxidative-stress-related cell damage is the preservation of the equilibrium between the production and scavenging of reactive oxygen.…”