Epidemiological studies suggest that consumption of vegetables rich in the xanthophylls lutein (LUT) and zeaxanthin (ZEA) reduces the risk for developing age-related cataract, a leading cause of vision loss. Although LUT and ZEA are the only dietary carotenoids present in the lens, direct evidence for their photoprotective effect in this organ is not available. The present study examined the effects of xanthophylls and alpha-tocopherol (alpha-TC) on lipid peroxidation and the mitogen-activated stress signaling pathways in human lens epithelial (HLE) cells following ultraviolet B light (UVB) irradiation. When presented with LUT, ZEA, astaxanthin (AST), and alpha-TC as methyl-beta-cyclodextrin complexes, HLE cells accumulated the lipophiles in a concentration- and time-dependent manner with uptake of LUT exceeding that of ZEA and AST. Pretreatment of cultures with either 2 micromol/L xanthophyll or 10 micromol/L alpha-TC for 4 h before exposure to 300 J/m(2) UVB radiation decreased lipid peroxidation by 47-57% compared with UVB-treated control HLE cells. Pretreatment with the xanthophylls and alpha-TC also inhibited UVB-induced activation of c-JUN NH(2)-terminal kinase (JNK) and p38 by 50-60 and 25-32%, respectively. There was substantial inhibition of UVB-induced JNK and p38 activation for cells containing <0.20 and approximately 0.30 nmol xanthophylls/mg, respectively, whereas >2.3 nmol alpha-TC/mg protein was required to significantly decrease UVB-induced stress signaling. These data suggest that xanthophylls are more potent than alpha-TC for protecting human lens epithelial cells against UVB insult.
Age-related macular degeneration (AMD) is the greatest cause of legal blindness in the western world. Established treatments include argon laser photocoagulation of extrafoveal choroidal neovascularisation (CNV) and photodynamic therapy of selected sub-foveal CNV. Newer approaches are targeting the angiogenic pathway in CNV development. Currently, other treatment modalities, such as radiotherapy and transpupillary thermotherapy do not have a clear role to play. Surgical options are experimental and only available in some centres for selected patients. Prevention of AMD remains elusive. Dietary supplements may have a role, while statins and prophylactic laser photocoagulation of drusen remain experimental. This paper explains the principles behind these approaches.
Macular pigments lutein and zeaxanthin as blue light filters studied in liposomes
(مطالعه رنگدانه های ماکولائی لوتئین و زاگزانتین در لیپوزوم ها بعنوان فیلتر نور آبی)
Junghans A, Sies H, Stahl W. Institut für Physiologische Chemie I and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany. Arch Biochem Biophys. 2001 Jul
Lutein and zeaxanthin are the predominant carotenoids in the human macula lutea. Epidemiological data suggest that an increased intake of a lutein-rich diet correlates with a diminished risk for age-related macular degeneration, a major cause of impaired vision in the elderly. Filtering of blue light has been proposed as a possible mechanism of protection. Here, the blue light filter efficacy of carotenoids was investigated in unilamellar liposomes loaded in the hydrophilic core space with a fluorescent dye, Lucifer yellow, excitable by blue light. Carotenoids were incorporated into the lipophilic membrane. Fluorescence emission in carotenoid-containing liposomes was lower than in carotenoid-free controls when exposed to blue light, indicating a filter effect. Filter efficacy was in the order lutein > zeaxanthin > beta-carotene > lycopene. Some of the difference in blue light filter efficacy of carotenoids is attributable to differences in extinction coefficients, and a major further contribution is suggested to be related to the orientation of the incorporated molecules in the liposomal membrane.
Neuroprotective Effect of an Antioxidant, Lutein, during Retinal Inflammation
(تاثیر محافظتی آنتی اکسیدان لوتئین بر اعصاب در التهاب شبکیه)
Mariko Sasaki, Yoko Ozawa, Toshihide Kurihara, Kousuke Noda,Yutaka Imamura, Saori Kobayashi,Susumu Ishida,and Kazuo Tsubota From the Laboratory of Retinal Cell Biology and theDepartment of Ophthalmology, Keio University School of Medicine, Tokyo , Japan ; andWakasa Seikatsu Co., Ltd., Kyoto, Japan .
PURPOSE. Lutein has been the focus of recent study as a possible therapeutic approach for retinal diseases, but the molecular mechanism of its neuroprotective effect remains to be elucidated. The aim of this study was to investigate, with the use of a mouse endotoxin-induced uveitis (EIU) model, the neuroprotective effects of lutein against retinal neural damage caused by inflammation.
METHODS. EIU was induced by intraperitoneal injection of lipopolysaccharide (LPS). Each animal was given a subcutaneous injection of lutein or vehicle three times: concurrently with and 3 hours before and after the LPS injection. Analysis was carried out 24 hours after EIU induction. Levels of rhodopsin protein and STAT3 activation were analyzed by immunoblotting. Lengths of the outer segments of the photoreceptor cells were measured. Dark-adapted full-field electroretinograms were recorded. Oxidative stress in the retina was analyzed by dihydroethidium and fluorescent probe. Expression of glial fibrillary acidic protein (GFAP) was shown immunohistochemically.
RESULTS. The EIU-induced decrease in rhodopsin expression followed by shortening of the outer segments and reduction in a-wave amplitude were prevented by lutein treatment. Levels of STAT3 activation, downstream of inflammatory cytokine signals, and reactive oxygen species (ROS), which are both upregulated during EIU, were reduced by lutein. Pathologic change of Müller glial cells, represented by GFAP expression, was also prevented by lutein.
CONCLUSIONS. The present data revealed that the antioxidant lutein was neuroprotective during EIU, suggesting a potential approach for suppressing retinal neural damage during inflammation
Nutritional and clinical relevance of lutein in human health.
(ارتباط بالینی و تغذیه ای لوتئین در سلامت انسان)
GranadoF,OlmedillaB,BlancoI. Servicio de Endocrinología y Nutricíon, Hospital Universitario Puerta de Hierro, Madrid, Spain
Lutein is one of the most widely found carotenoids distributed in fruits and vegetables frequently consumed. Its presence in human tissues is entirely of dietary origin. Distribution of lutein among tissues is similar to other carotenoids but, along with zeaxanthin, they are found selectively at the centre of the retina, being usually referred to as macular pigments. Lutein has no provitamin A activity in man but it displays biological activities that have attracted great attention in relation to human health. Epidemiological studies have shown inconsistent associations between high intake or serum levels of lutein and lower risk for developing cardiovascular disease, several types of cancer, cataracts and age-related maculopathy. Also, lutein supplementation has provided both null and positive results on different biomarkers of oxidative stress although it is effective in increasing macular pigment concentration and in improving visual function in some, but not all, subjects with different eye pathologies. Overall, data suggest that whereas serum levels of lutein have, at present, no predictive, diagnostic or prognostic value in clinical practice, its determination may be very helpful in assessing compliance and efficacy of intervention as well as potential toxicity. In addition, available evidence suggests that a serum lutein concentration between 0.6 and 1.05 micromol/l seems to be a safe, dietary achievable and desirable target potentially associated with beneficial impact on visual function and, possibly, on the development of other chronic diseases. The use of lutein as a biomarker of exposure in clinical practice may provide some rationale for assessing its relationship with human health as well as its potential use within the context of evidence-based medicine.
Lutein and Zeaxanthin Status and Risk of Age-Related Macular Degeneration
(ارتباط وضعیت لوتئین و زاگزانتیندر بدن با خطر ابتلا به بیماری AMD)
Catharine R. Gale, Nigel F. Hall, David I. W. Phillips, and Christopher N. Martyn Investigative Ophthalmology & Visual Science, June 2003
PURPOSE. To investigate the relation between plasma concentrations of lutein and zeaxanthin and age-related macular degeneration in a group of elderly men and women.
METHODS. The Wisconsin Age-Related Maculopathy Grading System was used to grade features of early and late macular degeneration in 380 men and women, aged 66 to 75 years, from Sheffield, United Kingdom . Fasting blood samples were taken to assess plasma concentrations of lutein and zeaxanthin.
RESULTS. Risk of age-related macular degeneration (early or late) was significantly higher in people with lower plasma concentrations of zeaxanthin. Compared with those whose plasma concentrations of zeaxanthin were in the highest third of the distribution, people whose plasma concentration was in the lowest third had an odds ratio for risk of age-related macular degeneration of 2.0 (95% confidence interval [CI] 1.0–4.1), after adjustment for age and other risk factors. Risk of agerelated macular degeneration was increased in people with the lowest plasma concentrations of lutein plus zeaxanthin (odds ratio [OR] 1.9, 95% CI 0.9 –3.5) and in those with the lowest concentrations of lutein (OR 1.7, 95% CI 0.9 –3.3), but neither of these relations was statistically significant.
CONCLUSIONS. These findings provide support for the view that zeaxanthin may protect against age-related macular degeneration.
Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye
(مکانیسم های بیولوژیک نقش محافظتی لوتئین و زاگزانتین در چشم)
Krinsky NI, Landrum JT, Bone RA. Department of Biochemistry, School of Medicine and the USDA Jean Mayer Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts Annu Rev Nutr. 2003 Feb
The macular region of the primate retina is yellow in color due to the presence of the macular pigment, composed of two dietary xanthophylls, lutein and zeaxanthin, and another xanthophyll, meso-zeaxanthin. The latter is presumably formed from either lutein or zeaxanthin in the retina. By absorbing blue-light, the macular pigment protects the underlying photoreceptor cell layer from light damage, possibly initiated by the formation of reactive oxygen species during a photosensitized reaction. There is ample epidemiological evidence that the amount of macular pigment is inversely associated with the incidence of age-related macular degeneration, an irreversible process that is the major cause of blindness in the elderly. The macular pigment can be increased in primates by either increasing the intake of foods that are rich in lutein and zeaxanthin, such as dark-green leafy vegetables, or by supplementation with lutein or zeaxanthin. Although increasing the intake of lutein or zeaxanthin might
process that is the major cause of blindness in the elderly. The macular pigment can be increased in primates by either increasing the intake of foods that are rich in lutein and zeaxanthin, such as dark-green leafy vegetables, or by supplementation with lutein or zeaxanthin. Although increasing the intake of lutein or zeaxanthin might prove to be protective against the development of age-related macular degeneration, a causative relationship has yet to be experimentally demonstrated.
The effects of supplementation with lutein and/or zeaxanthin on human macular pigment density and colour vision.
(تاثیر مکمل سازی لوتئین و زاگزانتین در مقدار رنگدانه ماکولائی انسان و دید رنگ ها )
Marisa Rodriguez-Carmona1, Jessica Kvansakul1, J Alister Harlow1, Wolfgang Ko¨pcke2, Wolfgang Schalch3 and John L Barbur1 Applied Vision Research Centre, The Henry Wellcome Laboratories for Vision Sciences, City .University, London, UK, 2University of Mu¨nster, Mu¨nster, Germany, and 3DSM Nutritional Products Ltd, Kaiseraugst, Switzerland Ophthal. Physiol. Opt. 2006
Background: Both yellow-blue (YB) discrimination thresholds and macular pigment optical density (MPOD) measurements in the eye exhibit large variability in the normal population. Although it is well established that selective absorption of blue light by the macular pigment (MP) can significantly affect trichromatic colour matches, the extent to which the MP affects colour discrimination (CD) sensitivity remains controversial.
Objective: In this study, we assess whether the variability in YB thresholds is attributable to differences in MPOD, both at the fovea and in the paracentral visual field. We also investigated whether higher levels of MP offer any advantage in other visual functions such as red-green (RG) CD sensitivity.
Design: CD thresholds and spatial MPOD profiles were measured in 24 normal trichromats supplemented with zeaxanthin (OPTISHARP_) and/or lutein. Novel stimulus conditions that isolate YB and RG chromatic mechanisms were employed and MPOD profiles were measured up to an eccentricity of 8_.
Results: The data reveal an increase in MPOD in the supplemented subjects that was almost uniform within a centre region around the fovea subtending ±4_. RG sensitivity was high in all subjects with thresholds well within the normal range. Unexpectedly, YB thresholds were also normal and showed no correlation with MPOD. A model for threshold CD based on appropriate combinations of cone contrast signals was developed to explain the experimental findings.
Conclusions: YB thresholds remain unaffected by supplementation with lutein and/or zeaxanthin rather, at increased MPOD levels, RG vision tends to be improved. The model accounts for the absence of correlation between MPOD and YB thresholds and predicts a marginal improvement in RG discrimination when MPOD is high.
