Two mechanisms for dissipation of excess light in monomeric and trimeric light-harvesting complexes.

Oxygenic photoautotrophs require mechanisms for rapidly matching the level of chlorophyll excited states from light harvesting with the rate of electron transport from water to carbon dioxide. These photoprotective reactions prevent formation of reactive excited states and photoinhibition. The fastest response to excess illumination is the so-called non-photochemical quenching which, in higher plants, requires the luminal pH sensor PsbS and other yet unidentified components of the photosystem II antenna. Both trimeric light-harvesting complex II (LHCII) and monomeric LHC proteins have been indicated as site(s) of the heat-dissipative reactions. Different mechanisms have been proposed: energy transfer to a lutein quencher in trimers, formation of a zeaxanthin radical cation in monomers. Here, we report on the construction of a mutant lacking all monomeric LHC proteins but retaining LHCII trimers. Its non-photochemical quenching induction rate was substantially slower with respect to the wild type. A carotenoid radical cation signal was detected in the wild type, although it was lost in the mutant. We conclude that non-photochemical quenching is catalysed by two independent mechanisms, with the fastest activated response catalysed within monomeric LHC proteins depending on both zeaxanthin and lutein and on the formation of a radical cation. Trimeric LHCII was responsible for the slowly activated quenching component whereas inclusion in supercomplexes was not required. This latter activity does not depend on lutein nor on charge transfer events, whereas zeaxanthin was essential.

Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease.

The human macula uniquely concentrates three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. Lutein and zeaxanthin must be obtained from dietary sources such as green leafy vegetables and orange and yellow fruits and vegetables, while meso-zeaxanthin is rarely found in diet and is believed to be formed at the macula by metabolic transformations of ingested carotenoids. Epidemiological studies and large-scale clinical trials such as AREDS2 have brought attention to the potential ocular health and functional benefits of these three xanthophyll carotenoids consumed through the diet or supplements, but the basic science and clinical research underlying recommendations for nutritional interventions against age-related macular degeneration and other eye diseases are underappreciated by clinicians and vision researchers alike. In this review article, we first examine the chemistry, biochemistry, biophysics, and physiology of these yellow pigments that are specifically concentrated in the macula lutea through the means of high-affinity binding proteins and specialized transport and metabolic proteins where they play important roles as short-wavelength (blue) light-absorbers and localized, efficient antioxidants in a region at high risk for light-induced oxidative stress. Next, we turn to clinical evidence supporting functional benefits of these carotenoids in normal eyes and for their potential protective actions against ocular disease from infancy to old age.

Lutein: more than just a filter for blue light.

Lutein is concentrated in the primate retina, where together with zeaxanthin it forms the macular pigment. Traditionally lutein is characterized by its blue light filtering and anti-oxidant properties. Eliminating lutein from the diet of experimental animals results in early degenerative signs in the retina while patients with an acquired condition of macular pigment loss (Macular Telangiectasia) show serious visual handicap indicating the importance of macular pigment. Whether lutein intake reduces the risk of age related macular degeneration (AMD) or cataract formation is currently a strong matter of debate and abundant research is carried out to unravel the biological properties of the lutein molecule. SR-B1 has recently been identified as a lutein binding protein in the retina and this same receptor plays a role in the selective uptake in the gut. In the blood lutein is transported via high-density lipoproteins (HDL). Genes controlling SR-B1 and HDL levels predispose to AMD which supports the involvement of cholesterol/lutein transport pathways. Apart from beneficial effects of lutein intake on various visual function tests, recent findings show that lutein can affect immune responses and inflammation. Lutein diminishes the expression of various ocular inflammation models including endotoxin induced uveitis, laser induced choroidal neovascularization, streptozotocin induced diabetes and experimental retinal ischemia and reperfusion. In vitro studies show that lutein suppresses NF kappa-B activation as well as the expression of iNOS and COX-2. Since AMD has features of a chronic low-grade systemic inflammatory response, attention to the exact role of lutein in this disease has shifted from a local effect in the eye towards a possible systemic anti-inflammatory function.

Características de la población con ingesta baja en luteína y zeaxantina en pacientes con degeneración macular asociada a la edad variante húmeda / Characteristics of patients with wet age-related macular degeneration and low intake of lutein and zeaxanthin

Objetivo: Averiguar las características de los pacientes con DMAE húmeda que ingieren suficiente luteína y zeaxantina en nuestra población. Métodos: Estudio protocolizado, prospectivo, observacional, transversal, en pacientes diagnosticados de DMAE húmeda activa. Se efectúa hemograma, perfil lipídico, y perfil hepático; una entrevista dietética sobre los hábitos alimentarios a partir de la realización de un recordatorio de 24h y estudio antropométrico. Se dividen en dos grupos en función de la ingesta de luteína-zeaxantina (L-Z).Grupo 1 (ingesta «suficiente»): pacientes con ingesta diaria ≥1.400mg/día en mujeres y 1.700mg/día en hombres (2/3 de la ingesta media diaria en población normal).Grupo 2: pacientes con ingesta diaria inferior a las del grupo 1. Se efectúa un estudio estadístico descriptivo y comparativo entre ambos grupos. Resultado: Un total de 52 pacientes, con una edad media de 78,9 años. Grupo 1: 11 pacientes (21% de la muestra). Grupo 2: 41. Los pacientes con ingesta suficiente de L-Z tienen mayor índice de masa corporal y perímetro de cintura. El 70-80% de los pacientes del grupo 1 presentan ingesta insuficiente de vitaminas A, C y E, y zinc. Conclusiones: El 79% de los pacientes tienen ingesta diaria de L-Z baja. Los pacientes con aporte suficiente tienen un aumento en el índice de masa corporal y perímetro de cintura, y además la mayoría tienen una ingesta insuficiente de vitaminas A, C y E, y zinc(AU)

Objective: To assess the characteristics of patients with wet AMD and low intake of lutein and zeaxanthin in our population. Methods: A prospective, observational, cross-sectional study was conducted on patients with active wet AMD. A full blood count, a lipid and liver profile, a dietary interview (24-hour recall), and an anthropometric study were performed. Lutein-zeaxanthin (LZ) intake results split the patents in two groups. Group 1 ("sufficient" intake): patients with ≥1,400mg/day intake in women and 1,700mg/day in men (2/3 of the average daily intake in a normal population). Group 2: patients with daily intakes below that of group 1. A descriptive and comparative statistical study was performed. Results: Fifty-two patients with a mean age of 78.9 years. Group 1: eleven patients (21% of the sample). Group 2: forty-one patients. The subjects with adequate intake of LZ had higher a body mass index and waist circumference. Between 70-80% of patients in group 1 had inadequate intake of vitamin A, C and E and zinc. Conclusions: Seventy-nine per cent of the patients with wet AMD have a deficient daily intake in lutein-zeaxanthin. The population with adequate intake is associated with an increased body mass index and waist circumference, and in addition, most of them have an insufficient intake of vitamin A, C, E and zinc(AU)

Lutein inhibits the function of the transient receptor potential A1 ion channel in different in vitro and in vivo models.

Transient receptor potential (TRP) ion channels, such as TRP vanilloid 1 and ankyrin repeat domain 1 (TRPV1 and TRPA1), are expressed on primary sensory neurons. Lutein, a natural tetraterpene carotenoid, can be incorporated into membranes and might modulate TRP channels. Therefore, the effects of the water-soluble randomly methylated-ß-cyclodextrin (RAMEB) complex of lutein were investigated on TRPV1 and TRPA1 activation. RAMEB-lutein (100 µM) significantly diminished Ca(2+) influx to cultured rat trigeminal neurons induced by TRPA1 activation with mustard oil, but not by TRPV1 stimulation with capsaicin, as determined with microfluorimetry. Calcitonin gene-related peptide release from afferents of isolated tracheae evoked by mustard oil, but not by capsaicin, was inhibited by RAMEB-lutein. Mustard oil-induced neurogenic mouse ear swelling was also significantly decreased by 100 µg/ml s.c. RAMEB-lutein pretreatment, while capsaicin-evoked edema was not altered. Myeloperoxidase activity indicating non-neurogenic granulocyte accumulation in the ear was not influenced by RAMEB-lutein in either case. It is concluded that lutein inhibits TRPA1, but not TRPV1 stimulation-induced responses on cell bodies and peripheral terminals of sensory neurons in vitro and in vivo. Based on these distinct actions and the carotenoid structure, the ability of lutein to modulate lipid rafts in the membrane around TRP channels can be suggested.

The effect of macular pigment on heterochromatic luminance contrast.

Macular pigment (MP) selectively filters short-wave light and may improve visual performance via this mechanism. This study was designed to test the hypothesis that MP alters contrast between an object and its background, and thus alters the object's detectability. In order to test this hypothesis, participants of a variety of ages were recruited into two groups. Group 1 consisted of 50 healthy elderly subjects (M = 72.7, SD = 7.3 years). Group 2 consisted of 28 healthy younger subjects (M = 22.7, SD = 3.6 years). For all subjects, contrast thresholds were assessed in Maxwellian-view. For subjects in Group 1, a circular grating target (600 nm, 1°; not absorbed by MP) was surrounded by a 10°, 460 nm field (strongly absorbed by MP). Subjects in Group 2 were measured using identical conditions with the exception that the surround was changed to 425 nm in one condition and to a broad-band (xenon) white in another. All subjects adjusted the intensity of the surround until the target was no longer visible. Finally, for a sub-sample of subjects in Group 2, a 1° bipartite field was used and wavelength was varied on one side to minimize the appearance of the border with the 460 nm reference side, foveally and parafoveally between 420-540 nm, with 20 nm steps, using the minimally distinct border (MDB) technique. MP density was assessed psychophysically. MP density was related to the amount of energy in the surround (at 425 and 460 nm, and for broad-band white) needed to lose sight of the central target. When the MDB technique was used to measure spectral sensitivity, the differences in the two curves yielded a spectrum that closely matched MP's ex vivo spectrum. Our data suggest that MP modifies an object's contrast against a short-wave background via simple filtration.

The relation between the macular carotenoids, lutein and zeaxanthin, and temporal vision.

Lutein (L) and zeaxanthin (Z) are the dominant carotenoids within the central retina (there, termed macular pigment, MP) and brain (approximately 70% of total carotenoid concentration). Past studies have shown that MP is related to many static indicators of visual performance, such as visibility and disability glare. It has also been shown that MP is related to a dynamic measure of visual performance, the critical flicker fusion threshold (CFF). In this study, we examine whether MP is related to CFF in a larger sample. We also test the relation between MP and the more complete temporal contrast sensitivity function (TCSF). A total of 70 participants were assessed for a comparison of MP and the full temporal function. A separate pool of 354 participants was assessed for a MP and CFF comparison. Peak MP density was measured psychophysically (via heterochromatic flicker photometry) using a 1-degree diameter test. CFF was measured using a 1-degree 570 nm test varied at 100% modulation. The full TCSF was measured centrally using a 1-degree, 660 nm test (the modulation depth of which could be adjusted directly by the subject) centered within a 5.5-degree, 660 nm surround. A small fixation point was used to test a 7-degree parafoveal site. MP density was positively related to temporal function as assessed by the full TCSF in the center (n = 70, r = -0.29, p < 0.01) but not at the parafoveal location (p < 0.07). MP was also positively related to critical flicker fusion thresholds (n = 354, r = 0.21, p < 0.0001).

Xanthophylls and eye health of infants and adults.

Lutein and zeaxanthin are the only carotenoids present in the eye. They cannot be synthesized de novo and are specifically concentrated in the macula. They appear to have at least two major functions: to filter out blue light and thus prevent ensuing damages to the eye and to act as antioxidants. Infants are particularly at risk from both blue light and oxidative damage to eye tissues. Lutein is present in human milk but is not currently added to infant formulas. Fortifying formulae with lutein in order to match more closely human milk might help protect the infant's sensitive eyes. In adults, the exact pathogenesis of age-related maculopathy remains unknown. Light damage, inflammation, and the disruption of cellular processes by oxidative stress may play an important role in the degenerative process. Manipulation of intake of xanthophylls has been shown to augment macular pigment, therefore it is thought that carotenoid dietary supplements could prevent, delay, or modify the course of age-related maculopathy. However, definite evidence of the effect of carotenoids, the optimal doses to use, and the supplementation duration are still under investigation.

Pigmentos maculares / Macular pigments

A luteína e a zeaxantina são pigmentos amarelos que se localizam na mácula. Devido à sua localização, diminuem e filtram a quantidade de luz principalmente azul que chega aos fotorreceptores, atuam como antioxidantes e podem melhorar a qualidade visual. Esta é uma revisão do seu mecanismo de incorporação, ação, possíveis aplicações e conhecimento científico a respeito.

Lutein and Zeaxanthin are yellow pigments located at the macula. Because of your location macular pigments decrease and filter the amount of blue light that reach photoreceptors, protect the outer retina from oxidative stress and may improve the vision quality. This is a review regarding incorporation mechanism, function and knowledge update.

Associations between lutein, zeaxanthin, and age-related macular degeneration: an overview.

Age-related macular degeneration, the leading cause of blindness in the elderly, is a degenerative condition of the macula characterized by death or dysfunction of the photoreceptors. With the aging population growing, the incidence of age-related macular degeneration is expected to increase. This raises concern about the future of visual dysfunction related falls and the resulting injuries in the elderly population. Lutein and zeaxanthin are macular pigments that may play a role in reducing the development and progression of age-related macular degeneration. Evidence is accumulating on the consumption of lutein and zeaxanthin (in whole food or supplemental form), the resulting concentrations in the serum, and tissue distribution throughout the body, particularly in the retina. Lutein and zeaxanthin intake increases serum concentrations which in turn increases macular pigment density. Existing literature focuses on factors affecting macular pigment density, functions of lutein and zeaxanthin as blue-light filters and antioxidants, and risk factors associated with age-related macular degeneration. Few studies have focused on the impact of dietary lutein and zeaxanthin on retinal function and the potential to preserve vision and prevent further degeneration. This presents an opportunity for further research to determine an effective dose that delays the progression of age-related macular degeneration.

Lutein and zeaxanthin in eye and skin health.

Less than 20 of the hundreds of carotenoids found in nature are found in the human body. These carotenoids are present in the body from the foods or dietary supplements that humans consume. The body does not synthesize them. Among the carotenoids present in the body, only lutein and its coexistent isomer, zeaxanthin, are found in that portion of the eye where light is focused by the lens, namely, the macula lutea. Numerous studies have shown that lutein and zeaxanthin may provide significant protection against the potential damage caused by light striking this portion of the retina. In the eye, lutein and zeaxanthin have been shown to filter high-energy wavelengths of visible light and act as antioxidants to protect against the formation of reactive oxygen species and subsequent free radicals. Human studies have demonstrated that lutein and zeaxanthin are present in the skin, and animal studies have provided evidence of significant efficacy against light-induced skin damage, especially the ultraviolet wavelengths. Little was known about the protective effects of these carotenoids in human skin until recently. This article reviews the scientific literature pertaining to the effects that lutein and zeaxanthin exhibit in the human eye and skin.

[Macular pigments]. / Pigmentos maculares.

Lutein and Zeaxanthin are yellow pigments located at the macula. Because of your location macular pigments decrease and filter the amount of blue light that reach photoreceptors, protect the outer retina from oxidative stress and may improve the vision quality. This is a review regarding incorporation mechanism, function and knowledge update.

[Lutein and eye health--current state of discussion]. / Lutein und Augengesundheit. Stand der Diskussion.

Due to increased life expectancy the number of people with age-related diseases like age-related macular degeneration (AMD) will grow. Currently AMD is incurable and only a few therapeutic strategies are available. Therefore prevention becomes more important. Protective effects related to eye health are discussed for the two carotenoids lutein and zeaxanthin. Meanwhile both substances are offered as food supplements to a great extent. Both carotenoids lutein and zeaxanthin are accumulated in the retina, especially in the macula lutea. They are able to absorb blue light, which damages photoreceptors and pigmentary epithelium. Due to their antioxidative properties they can reduce changes in membrane permeability via quenching reactive oxygen species and free radicals. Research studies suppose lutein and zeaxanthin may contribute to improvement of vision in patients with AMD and other eye diseases. Based on the scientific rationale, these carotenoids may be effective in the prevention of age-related eye diseases. However, this issue has to be examined in a differentiated way.

The role of lutein in the acclimation of higher plant chloroplast membranes to suboptimal conditions.

Two mutants of Arabidopsis thaliana deficient in lutein have been investigated with respect to their responses to growth under a range of suboptimal conditions. The first mutant, lut1, was enriched in violaxanthin, antheraxanthin, zeaxanthin and zeinoxanthin compared with the wild-type (WT). In the second mutant, lut2, the lack of lutein was compensated for only by an increase in xanthophyll cycle (XC) carotenoids. Upon transfer of plants grown under optimal conditions to high light (HL), drought or HL + drought, both mutants acclimated during several days to the new conditions to the same extent as the WT. In contrast, transfer to chilling conditions (6 degrees C) for 6 days induced responses that were different between WT and mutants and between the mutants themselves. In contrast to the WT, the lut2 mutant in particular exhibited a large increase in the Chl a/b ratio and the XC pool size, extensive de-epoxidation and an enhanced extent of non-photochemical quenching. It is suggested that although the role of lutein in the structure and organisation of the light-harvesting complexes can be fulfilled by other xanthophylls under excess light conditions at optimal temperatures, this is not the case at low temperature.

[Protective role of lutein on light-damage of retina].

Lutein may be a member of the xanthophy II of carotenoids. It could be a non-provitamin A xanthophy II, which was different from other carotenoids. Lutein and zeaxanthin composed the macular pigments, which were found in the retina. The protective mechanism of lutein in the retina could possibly be in two important ways: the first function could relate to filtering blue light, and the second could consider to be the antioxidative activity that could quench and scavenge reactive oxygen species(ROS) induced by light. The structure and source of lutein, and association between lutein and retina macular pigment, and the role and mechanism of lutein in protecting the retina from light damage were reviewed.

Macular pigment and visual performance under glare conditions.

PURPOSE: Many parameters of visual performance (e.g., contrast sensitivity) are compromised under glaring light conditions. Recent data indicate that macular pigment (MP) is strongly related to improvements in glare disability and photostress recovery based on a filtering mechanism. In this study, we assessed the causality of this relation by supplementing lutein and zeaxanthin for 6 months while measuring MP, glare disability, and photostress recovery. METHODS: Forty healthy subjects (mean age = 23.9) participated in the study. Subjects were followed for 6 months and assessed at baseline, 1, 2, 4, and 6 months. Spatial density profiles of MP were measured using heterochromatic flicker photometry. Disability glare was measured using a 1 degree-diameter circular grating surrounded by a broadband glare source (a xenon-white annulus). The intensity of the annulus (11 degree inner and 12 degree outer diameters) was adjusted by the subject until the grating target was no longer seen. For the photostress recovery experiment, the time required to detect a 1 degree-diameter grating stimulus after a 5-s exposure to a 2.5 muW/cm2, 5 degree-diameter disk was recorded. Subjects were tested under central viewing and eccentric viewing (10 degree temporal retina) conditions. RESULTS: At the baseline time point, MP optical density (OD) at 30' eccentricity ranged from 0.08 to 1.04, and was strongly correlated with improved visual performance in the two glare tasks. After 6 months of lutein (L) and zeaxanthin (Z) supplementation, average MPOD (at 30' eccentricity) had increased from 0.41 to 0.57, and was shown to significantly reduce the deleterious effects of glare for both the visual performance tasks assessed. CONCLUSIONS: MP is strongly related to improvements in glare disability and photostress recovery in a manner strongly consistent with its spectral absorption and spatial profile. Four to 6 months of 12 mg daily L + Z supplementation significantly increases MPOD and improves visual performance in glare for most subjects.

Lutein is needed for efficient chlorophyll triplet quenching in the major LHCII antenna complex of higher plants and effective photoprotection in vivo under strong light.

BACKGROUND: Lutein is the most abundant xanthophyll in the photosynthetic apparatus of higher plants. It binds to site L1 of all Lhc proteins, whose occupancy is indispensable for protein folding and quenching chlorophyll triplets. Thus, the lack of a visible phenotype in mutants lacking lutein has been surprising. RESULTS: We have re-assessed the lut2.1 phenotypes through biochemical and spectroscopic methods. Lhc proteins from the lut2.1 mutant compensate the lack of lutein by binding violaxanthin in sites L1 and L2. This substitution reduces the capacity for regulatory mechanisms such as NPQ, reduces antenna size, induces the compensatory synthesis of Antheraxanthin + Zeaxanthin, and prevents the trimerization of LHCII complexes. In vitro reconstitution shows that the lack of lutein per se is sufficient to prevent trimerization. lut2.1 showed a reduced capacity for state I-state II transitions, a selective degradation of Lhcb1 and 2, and a higher level of photodamage in high light and/or low temperature, suggesting that violaxanthin cannot fully restore chlorophyll triplet quenching. In vitro photobleaching experiments and time-resolved spectroscopy of carotenoid triplet formation confirmed this hypothesis. The npq1lut2.1 double mutant, lacking both zeaxanthin and lutein, is highly susceptible to light stress. CONCLUSION: Lutein has the specific property of quenching harmful 3Chl* by binding at site L1 of the major LHCII complex and of other Lhc proteins of plants, thus preventing ROS formation. Substitution of lutein by violaxanthin decreases the efficiency of 3Chl* quenching and causes higher ROS yield. The phenotype of lut2.1 mutant in low light is weak only because rescuing mechanisms of photoprotection, namely zeaxanthin synthesis, compensate for the ROS production. We conclude that zeaxanthin is effective in photoprotection of plants lacking lutein due to the multiple effects of zeaxanthin in photoprotection, including ROS scavenging and direct quenching of Chl fluorescence by binding to the L2 allosteric site of Lhc proteins.

Photooxidation of A2-PE, a photoreceptor outer segment fluorophore, and protection by lutein and zeaxanthin.

A2-PE is a pigment that forms as a byproduct of the visual cycle, its synthesis from all-trans-retinal and phosphatidylethanolamine occurring in photoreceptor outer segments. A2-PE is deposited in retinal pigment epithelial (RPE) cells secondary to phagocytosis of shed outer segment membrane and it undergoes hydrolysis to generate the RPE lipofuscin fluorophores, A2E, iso-A2E and other minor cis-isomers of A2E. We have demonstrated that A2-PE can initiate photochemical processes that involve the oxidation of A2-PE and that, by analogy with A2E are likely to include the formation of reactive moieties. We also show that potential sources of protection against the photooxidation of A2-PE are the lipid-soluble carotenoids zeaxanthin and lutein (xanthophylls), that constitute the yellow pigment of the macula. Irradiation of A2-PE in the presence of lutein or zeaxanthin suppressed A2-PE photooxidation and in experiments in which we compared the antioxidant capability of zeaxanthin and lutein to alpha-tocopherol, the carotenoids were more potent. Additionally, the effect with zeaxanthin was consistently more robust than with lutein and when alpha-tocopherol was combined with either carotenoid, the outcome was additive. Lutein, zeaxanthin and alpha-tocopherol were all efficient quenchers of singlet oxygen. We have also shown that lutein and zeaxanthin can protect against A2-PE/A2E photooxidation without appreciable consumption of the carotenoid by chemical reaction. This observation contrasts with the pronounced susceptibility of A2E and A2-PE to photooxidation and is of interest since lutein, zeaxanthin, A2E and A2-PE all have conjugated systems of carbon-carbon double bonds terminating in cyclohexenyl end-groups. The structural features responsible for the differences in quenching mechanisms are discussed. It has long been suspected that macular pigment protects the retina both by filtering high-energy blue light and by serving an antioxidant function. Evidence presented here suggests that the photochemical reactions against which lutein and zeaxanthin protect, may include those initiated by the A2-PE. Quantitative HPLC analysis revealed that in eyecups of C57BL/6J and BALB/cByJ mice, levels of A2-PE were several fold greater than the cleavage product, A2E. Taken together, these results may have implications with respect to the involvement of A2-PE formation in mechanisms underlying blue light-induced photoreceptor cell damage and may be significant to retinal degenerative disorders, such as those associated with ABCA4 mutations, wherein there is a propensity for increased A2-PE synthesis.