Macular Pigment Optical Density and Skin Carotenoids in a Childhood Sample.

BACKGROUND: Carotenoids are plant pigments with light filtering and antioxidant properties that deposit in human tissues, including retina and skin. Descriptive characteristics and covariates of carotenoid status in macula and skin have been examined in adults; however, similar studies in children are limited. Thus, this study aimed to delineate how factors of age, sex, race, weight status, and dietary carotenoid intake relate to macular and skin carotenoids in children. METHODS: Children (7-13 y, N = 375) completed heterochromatic flicker photometry to assess macular pigment optical density (MPOD). Participants underwent anthropometrics to measure weight status (BMI percentile [BMI%]), and parent/guardian provided demographic information. Subsample data were available for skin carotenoids (N = 181), assessed using reflection spectroscopy, and dietary carotenoids (N = 101) using the Block Food Frequency Questionnaire. Relationships between skin and macular carotenoids were assessed using partial Pearson's correlations controlling for age, sex, race, and BMI%. Relationships between dietary carotenoids and macular and skin carotenoids were assessed using stepwise linear regression including age, sex, race, and BMI% in the model. RESULTS: Mean MPOD was 0.56 ± 0.22 and skin carotenoid score was 282 ± 94.6. There was no significant correlation between MPOD and skin carotenoids (r = 0.02, P = 0.76). BMI% was negatively associated with skin (stdß = -0.42, P < 0.001), but not macular carotenoids (stdß = -0.04, P = 0.70). Neither MPOD nor skin carotenoids were associated with age, sex, or race (all P > 0.10). MPOD was positively associated with energy-adjusted reported lutein + zeaxanthin intake (stdß = 0.27, P = 0.01). Skin carotenoids were positively associated with energy-adjusted reported carotenoid intake (stdß = 0.26, P = 0.01). CONCLUSIONS: The mean MPOD values in children were higher than what has been reported in adult populations. Previous studies in adult samples report an average MPOD of 0.21. Although macular and skin carotenoids were not related, they were associated with dietary carotenoids relevant to the respective tissues; however, skin carotenoids may be more susceptible negative influence from higher weight status.

Physiological Significance of the Heterogeneous Distribution of Zeaxanthin and Lutein in the Retina of the Human Eye.

Zeaxanthin and lutein are xanthophyll pigments present in the human retina and particularly concentrated in its center referred to as the yellow spot (macula lutea). The fact that zeaxanthin, including its isomer meso-zeaxanthin, is concentrated in the central part of the retina, in contrast to lutein also present in the peripheral regions, raises questions about the possible physiological significance of such a heterogeneous distribution of macular xanthophylls. Here, we attempt to address this problem using resonance Raman spectroscopy and confocal imaging, with different laser lines selected to effectively distinguish the spectral contribution of lutein and zeaxanthin. Additionally, fluorescence lifetime imaging microscopy (FLIM) is used to solve the problem of xanthophyll localization in the axon membranes. The obtained results allow us to conclude that one of the key advantages of a particularly high concentration of zeaxanthin in the central part of the retina is the high efficiency of this pigment in the dynamic filtration of light with excessive intensity, potentially harmful for the photoreceptors.

Biochemical and Immunological implications of Lutein and Zeaxanthin.

Throughout history, nature has been acknowledged for being a primordial source of various bioactive molecules in which human macular carotenoids are gaining significant attention. Among 750 natural carotenoids, lutein, zeaxanthin and their oxidative metabolites are selectively accumulated in the macular region of living beings. Due to their vast applications in food, feed, pharmaceutical and nutraceuticals industries, the global market of lutein and zeaxanthin is continuously expanding but chemical synthesis, extraction and purification of these compounds from their natural repertoire e.g., plants, is somewhat costly and technically challenging. In this regard microbial as well as microalgal carotenoids are considered as an attractive alternative to aforementioned challenges. Through the techniques of genetic engineering and gene-editing tools like CRISPR/Cas9, the overproduction of lutein and zeaxanthin in microorganisms can be achieved but the commercial scale applications of such procedures needs to be done. Moreover, these carotenoids are highly unstable and susceptible to thermal and oxidative degradation. Therefore, esterification of these xanthophylls and microencapsulation with appropriate wall materials can increase their shelf-life and enhance their application in food industry. With their potent antioxidant activities, these carotenoids are emerging as molecules of vital importance in chronic degenerative, malignancies and antiviral diseases. Therefore, more research needs to be done to further expand the applications of lutein and zeaxanthin.

Mechanisms enhancing the protective functions of macular xanthophylls in the retina during oxidative stress.

Macular xanthophylls (MXs) are distinguished from other dietary carotenoids by their high membrane solubility and preferential transmembrane orientation. Additionally, these properties enhance the chemical and physical stability of MXs in the eye retina, and maximize their protective activities. The effectiveness of MXs' protection is also enhanced by their selective accumulation in the most vulnerable domains of retinal membranes. The retina is protected by MXs mainly through blue-light filtration, quenching of the excited triplet states of potent photosensitizers, and physical quenching of singlet oxygen. To perform these physical, photo-related actions, the structure of MXs should remain intact. However, the conjugated double-bond structure of MXs makes them highly chemically reactive and susceptible to oxidation. Chemical quenching of singlet oxygen and scavenging of free radicals destroy their intact structure and consume MXs. Consequently, their physical actions, which are critical to the protection of retina, are diminished. Thus, it is timely and important to identify mechanisms whereby the chemical destruction (bleaching) of MXs in retinal membranes can be reduced. It was shown that nitroxide free radicals (spin labels) located in membranes protect MXs against destruction, and their effect is especially pronounced during the light-induced formation of singlet oxygen. That should extend and enhance their positive action in the retina through physical processes. In this review, we will discuss possible applications of this new strategy during ophthalmological procedures, which can cause acute bleaching of MXs and damage the retina through oxidative processes.

Evidence of macular pigment in the central macula in albinism.

PURPOSE: Albinism represents a spectrum of disorders with diminished to absent amounts of melanin pigmentation including the posterior segment of the eye. Macular pigment (MP) consists of two main carotenoids, lutein and zeaxanthin, concentrated in the macula. MP serves as blue light absorbent, antioxidant, and may reduce chromatic aberration and glare. It remains unclear if albinos have detectable MP. The purpose was to investigate the distribution of MP in albino patients with psychophysical and imaging techniques. METHODS: MP was measured at the eccentricity of 0.5° by heterochromatic flicker perimetry (QuantifEye(®); Tinsley Precision Instruments Ltd.) or by scanning laser ophthalmoscopy (MPOD module, MultiColor Spectralis(®), Heidelberg Engineering, Heidelberg, Germany) in four albino patients, who were also investigated with multimodal ophthalmic imaging. RESULTS: Visual acuity ranged from 20/32 to 20/125, nystagmus was present in three patients, and all patients showed typical foveal hypoplasia on fundus exam and optical coherence tomography. Fundus autofluorescence (FAF) demonstrated various degrees of central FAF signal attenuation. Genetic testing was available in three patients and confirmed the diagnosis. Measurable amounts of MP were detected in all four patients and ranged from 0.05 to 0.24, which is below the normal range. CONCLUSIONS: We conclude that MP can be demonstrated and measured in albinos. Further studies are needed to investigate MP accumulation following carotenoid supplementation and its impact on visual performance.

Solubilization and stabilization of macular carotenoids by water soluble oligosaccharides and polysaccharides.

Xanthophyll carotenoids zeaxanthin and lutein play a special role in the prevention and treatment of visual diseases. These carotenoids are not produced by the human body and must be consumed in the diet. On the other hand, extremely low water solubility of these carotenoids and their instability restrict their practical application as components of food or medicinal formulations. Preparation of supramolecular complexes of zeaxanthin and lutein with glycyrrhizic acid, its disodium salt and the natural polysaccharide arabinogalactan allows one to minimize the aforementioned disadvantages when carotenoids are used in food processing as well as for production of therapeutic formulations with enhanced solubility and stability. In the present study, the formation of supramolecular complexes was investigated by NMR relaxation, surface plasmon resonance (SPR) and optical absorption techniques. The complexes increase carotenoid solubility more than 1000-fold. The kinetics of carotenoid decay in reactions with ozone molecules, hydroperoxyl radicals and metal ions were measured in water and organic solutions, and significant increases in oxidation stability of lutein and zeaxanthin in arabinogalactan and glycyrrhizin complexes were detected.

Association of macular pigment optical density with serum concentration of oxidized low-density lipoprotein in healthy adults.

PURPOSE: To analyze the association between macular pigment optical density (MPOD), which reflects lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) in the macula, and background characteristics. METHODS: Fifty-five healthy adult volunteers were analyzed. Macular pigment optical density was measured using a heterochromatic flicker photometry technique, and serum concentrations of carotenoids and lipoproteins were by high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. Dietary intake of nutrient was determined by a validated self-administered questionnaire on ingestion frequency. RESULTS: Macular pigment optical density was positively correlated with serum concentrations of L and Z and dietary L intake and inversely correlated with serum oxidized low-density lipoprotein (LDL). Although MPOD decreased with age (95% confidence interval, -0.011 to -0.002; correlation coefficient, -0.269; P = 0.007), serum L/Z and dietary L intake did not. In contrast, serum oxidized LDL was positively correlated with age (95% confidence interval, 0.69-2.34; correlation coefficient, 0.333; P = 0.0004). After adjusting for age, sex, and oxidized LDL, serum L was positively correlated with MPOD (95% confidence interval, 0.88-1.69; P = 0.000001). After adjusting for age, sex, and serum L, serum oxidized LDL was inversely correlated with MPOD (95% confidence interval, -0.002 to -0.0004; P = 0.006). CONCLUSION: Macular pigment optical density was inversely correlated with serum oxidized LDL. Further study to know the impact of oxidized LDL on MPOD may be warranted.

Macular pigment optical density is related to cognitive function in older people.

BACKGROUND: the xanthophylls lutein (L) and zeaxanthin (Z) exist in relatively high concentration in multiple central nervous tissues (e.g. cortex and neural retina). L + Z in macula (i.e. macular pigment, MP) are thought to serve multiple functions, including protection and improvement of visual performance. Also, L + Z in the macula are related to L + Z in the cortex. OBJECTIVE: to determine whether macular pigment optical density (MPOD, L + Z in the macula) is related to cognitive function in older adults. METHODS: participants were older adults (n = 108, 77.6 ± 2.7 years) sampled from the age-related maculopathy ancillary study of the Health Aging and Body Composition Study (Memphis, TN, USA). Serum carotenoids were measured using high performance liquid chromatography. MPOD was assessed using heterochromatic flicker photometry. Eight cognitive tests designed to evaluate several cognitive domains including memory and processing speed were administered. Partial correlation coefficients were computed to determine whether cognitive measures were related to serum L + Z and MPOD. RESULTS: MPOD levels were significantly associated with better global cognition, verbal learning and fluency, recall, processing speed and perceptual speed, whereas serum L + Z was significantly related to only verbal fluency. CONCLUSION: MPOD is related to cognitive function in older people. Its role as a potential biomarker of cognitive function deserves further study.

Concordance of macular pigment measurements obtained using customized heterochromatic flicker photometry, dual-wavelength autofluorescence, and single-wavelength reflectance.

This study compares in vivo measurements of macular pigment (MP) obtained using customized heterochromatic flicker photometry (cHFP; Macular Metrics Densitometer(™)), dual-wavelength fundus autofluorescence (Heidelberg Spectralis(®) HRA + OCT MultiColor) and single-wavelength fundus reflectance (Zeiss Visucam(®) 200). MP was measured in one eye of 62 subjects on each device. Data from 49 subjects (79%) was suitable for analysis. Agreement between the Densitometer and Spectralis was investigated at various eccentricities using a variety of quantitative and graphical methods, including: Pearson correlation coefficient to measure degree of scatter (precision), accuracy coefficient, concordance correlation coefficient (ccc), paired t-test, scatter and Bland-Altman plots. The relationship between max MP from the Visucam and central MP from the Spectralis and Densitometer was investigated using regression methods. Agreement was strong between the Densitometer and Spectralis at all central eccentricities (e.g. at 0.25° eccentricity: accuracy = 0.97, precision = 0.90, ccc = 0.87). Regression analysis showed a very weak relationship between the Visucam and Densitometer (e.g. Visucam max on Densitometer central MP: R(2) = 0.008, p = 0.843). Regression analysis also demonstrated a weak relationship between MP measured by the Spectralis and Visucam (e.g. Visucam max on Spectralis central MP: R(2) = 0.047, p = 0.348). MP values obtained using the Heidelberg Spectralis are comparable to MP values obtained using the Densitometer. In contrast, MP values obtained using the Zeiss Visucam are not comparable with either the Densitometer or the Spectralis MP measuring devices. Taking cHFP as the current standard to which other MP measuring devices should be compared, the Spectralis is suitable for use in a clinical and research setting, whereas the Visucam is not.

Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates.

OBJECTIVES: Xanthophyll pigments lutein and zeaxanthin cross the blood-retina barrier to preferentially accumulate in the macular region of the neural retina. There they form macular pigment, protecting the retina from blue light damage and oxidative stress. Lutein and zeaxanthin also accumulate in brain tissue. The objective of the study was to evaluate the relationship between retinal and brain levels of these xanthophylls in non-human primates. METHODS: Study animals included rhesus monkeys reared on diets devoid of xanthophylls that were subsequently fed pure lutein or pure zeaxanthin (both at 3.9 µmol/kg per day, n = 6/group) and normal rhesus monkeys fed a stock diet (0.26 µmol/kg per day lutein and 0.24 µmol/kg per day zeaxanthin, n = 5). Retina (4 mm macular punch, 4-8 mm annulus, and periphery) and brain tissue (cerebellum, frontal cortex, occipital cortex, and pons) from the same animals were analyzed by reverse-phase high-performance liquid chromatography. RESULTS: Lutein in the macula and annulus was significantly related to lutein levels in the cerebellum, occipital cortex, and pons, both in bivariate analysis and after adjusting for age, sex and n-3 fatty acid status. In the frontal cortex the relationship was marginally significant. Macular zeaxanthin was significantly related to zeaxanthin in the cerebellum and frontal cortex, while the relationship was marginally significant in the occipital cortex and pons in a bivariate model. DISCUSSION: An integrated measure of total macular pigment optical density, which can be measured non-invasively, has the potential to be used as a biomarker to assess brain lutein and zeaxanthin status.

The microstructural and functional changes in the macula of heavy habitual smokers.

To investigate whether heavy habitual smoking affects microstructures and functions of the macula, 45 age- (20-39 years old) and sex-matched adult smokers (≥1 box/day for ≥5 years) and 45 nonsmokers (controls) were enrolled in this case-control study. Central macular thickness (CMT), macular autofluorescent pigment density (MAPD), macular electroretinogram (ERG), and photostress recovery time (PRT) measurements were performed. The mean age of smokers and nonsmokers was 32.9 ± 3.9 and 33.1 ± 4.1 years, respectively (p = 0.43), and smoking duration was 11 ± 5.6 years. CMT in smokers (220 ± 28 µm) and nonsmokers (217.2 ± 31 µm; p = 0.57) was similar. Smokers had lower MAPD values (124.6) than nonsmokers (138.2) (p = 0.010). Multifocal ERG parameters in the central (6°) hexagon were similar in both groups (p > 0.05 for latency and amplitudes of P1 and N1). PRT in smokers and nonsmokers was similar (7.2 ± 1.2 and 7.4 ± 1.9 min, respectively; p = 0.33); however, foveal threshold value (FTV) at the first minute after photostress was statistically higher in smokers (36.1 ± 1.04 dB) than nonsmokers (34.8 ± 1.05 dB) (p = 0.011). We conclude that decreased MAPD and altered response to photostress may be indicative of early nicotine toxicity in microstructurally sound macula of adult chronic smokers.

Measuring macular pigment optical density in vivo: a review of techniques.

BACKGROUND: Macular pigment has been the focus of much attention in recent years, as a potential modifiable risk factor for age-related macular degeneration. This interest has been heightened by the ability to measure macular pigment optical density (MPOD) in vivo. METHOD: A systematic literature search was undertaken to identify all available papers that have used in vivo MPOD techniques. The papers were reviewed, and all relevant information was incorporated into this article. RESULTS: Measurement of MPOD is achievable with a wide range of techniques, which are typically categorized into one of two groups: psychophysical (requiring a response from the subject) or objective (requiring minimal input from the subject). The psychophysical methods include heterochromatic flicker photometry and minimum motion photometry. The objective methods include fundus reflectometry, fundus autofluorescence, resonance Raman spectroscopy and visual evoked potentials. Even within the individual techniques, there is often much variation in how data is obtained and processed. CONCLUSION: This review comprehensively details the procedure, instrumentation, assumptions, validity and reliability of each MPOD measurement technique currently available, along with their respective advantages and disadvantages. This leads us to conclude that development of a commercial instrument, based on fundus reflectometry or fundus autofluorescence, would be beneficial to macular pigment research and would support MPOD screening in a clinical setting.

Macular Pigment Reflectometry: Developing Clinical Protocols, Comparison with Heterochromatic Flicker Photometry and Individual Carotenoid Levels.

The study was designed to: (1) Analyze and create protocols of obtaining measurements using the Macular Pigment Reflectometry (MPR). (2) To assess the agreement of MPOD measurements obtained using the heterochromatic flicker photometry (MPS II) and MPR. (3) To obtain the lutein and zeaxanthin optical density obtained using the MPR in the central one-degree of the macula. The measurements were performed using the MPR and heterochromatic flicker photometry. The MPR measurements were performed twice without pupillary dilation and twice following pupillary dilation. The MPR measurements were performed for a 40-s period and the spectrometer signal was parsed at different time points: 10-20, 10-30, 10-40, 20-30, 20-40, and 30-40 s. The MPR analyzes the high-resolution spectrometer signal and calculates MPOD, lutein optical density and zeaxanthin optical density automatically. The MPR-MPOD data was compared with MPPS II-MPOD results. The MPR-MPOD values are highly correlated and in good agreement with the MPS II-MPOD. Of the various parsing of the data, the data 10-30 interval was the best at obtaining the MPOD, lutein, and zeaxanthin values (8-12% coefficient of repeatability). The lutein to zeaxanthin ratio in the central one-degree of the macula was 1:2.40. Dilation was not needed to obtain the MPOD values but provided better repeatability of lutein and zeaxanthin optical density. MPR generates MPOD measurements that is in good agreement with MPS II. The device can produce lutein and zeaxanthin optical density which is not available from other clinical devices.

The Macular Assessment Profile test - a new VDU-based technique for measuring the spatial distribution of the macular pigment, lens density and rapid flicker sensitivity.

The measurement of macular pigment optical density (MPOD) in the eye is often carried out using optical techniques based on heterochromatic flicker photometry (HFP). These require the use of two spectrally-narrow beams, one at the wavelength of maximum absorption of the macular pigment (MP) and the other in the long wavelength region of the visible spectrum where MP absorption is negligible. A new technique for the measurement of MPOD spatial profiles has been developed by overcoming the current shortcomings associated with the use of visual displays. The new Macular Assessment Profile (MAP) test makes use of a 'notch' filter and a photometric model to measure and compute the peak MPOD value. Two other useful parameters are also computed from the same measurements. These describe the subject's sensitivity to rapid flicker and the absorption of blue light by the lens. MPOD profiles, lens density, rapid flicker sensitivity, and red/green (RG) and yellow/blue (YB) colour thresholds were measured in 54 normal subjects aged 18-61 years. The results confirm previous findings on ageing effects and demonstrate the complete absence of correlation between MPOD and the subject's YB chromatic thresholds. In contrast, RG chromatic sensitivity improves with higher levels of MPOD.

Simulations of adaptation and color appearance in observers with varying spectral sensitivity.

A model of adaptation and visual coding was used to simulate how color appearance might vary among individuals that differ only in their sensitivity to wavelength. Color responses to images were calculated for cone receptors with spectral sensitivities specific to the individual, and in postreceptoral mechanisms tuned to different combinations of the cones. Adaptation was assumed to normalize sensitivity within each cone and postreceptoral channel so that the average response to an ensemble of scenes equaled the mean response in channels defined for the reference observer. Image colors were then rendered from the adapted channels' outputs. The transformed images provide an illustration of the variations in color appearance that could be attributed to differences in spectral sensitivity in otherwise identical observers adapted to identical worlds, and examples of these predictions are shown for both normal variation (e.g. in lens and macular pigment) and color deficiencies (anomalous trichromacy). The simulations highlight the role that known processes of adaptation may play in compensating color appearance for variations in sensitivity both within and across observers, and provide a novel tool for visualizing the perceptual consequences of any variation in visual sensitivity including changes associated with development or disease.

Effect of an antioxidant supplement containing high dose lutein and zeaxanthin on macular pigment and skin carotenoid levels.

The effect of a high dose lutein/zeaxanthin supplement on macular pigment optical density (MPOD) and skin carotenoid (SC) levels in healthy subjects was investigated. This is a prospective, single-arm, open-label study. Subjects were 16 Japanese, age 26-57 years. Subjects took a supplement containing 20 mg/day of lutein, 4 mg/day of zeaxanthin, and other antioxidants (vitamin C, vitamin E, zinc, copper) for 16 weeks. MPOD levels were measured by a two-wavelength autofluorescence imaging technique. SC levels were measured by reflection spectroscopy. Total volume of MPOD within 9° eccentricity significantly increased by week 8 and continued to increase until week 16 (p < 0.0001, two-way factorial ANOVA). The increase rate of MPOD was significantly higher in subjects with body mass index (BMI) less than 25 kg/m2 (n = 13) compared to those of 25 kg/m2 and higher (n = 3). SC levels increased significantly by week 4 and continued to increase until week 16 (p < 0.0001, two-way factorial ANOVA). All subjects completed the study without any serious adverse events. These results demonstrated the effectiveness of a high dose lutein/zeaxanthin supplement for MPOD volume and SC levels without serious adverse events.

Lutein Supplementation for Eye Diseases.

Lutein is one of the few xanthophyll carotenoids that is found in high concentration in the macula of human retina. As de novo synthesis of lutein within the human body is impossible, lutein can only be obtained from diet. It is a natural substance abundant in egg yolk and dark green leafy vegetables. Many basic and clinical studies have reported lutein's anti-oxidative and anti-inflammatory properties in the eye, suggesting its beneficial effects on protection and alleviation of ocular diseases such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, myopia, and cataract. Most importantly, lutein is categorized as Generally Regarded as Safe (GRAS), posing minimal side-effects upon long term consumption. In this review, we will discuss the chemical structure and properties of lutein as well as its application and safety as a nutritional supplement. Finally, the effects of lutein consumption on the aforementioned eye diseases will be reviewed.

Quantification of reduced macular pigment optical density in the central retina in macular telangiectasia type 2.

Recently, a unique distribution, namely a reduction of macular pigment optical density (MPOD) within the central retina with a surrounding ring-like structure of preserved MPOD at about 6 degrees eccentricity was suggested to be a common finding in macular telangiectasia (MacTel) type 2. In order to quantify this reduced MPOD, 28 eyes of 14 patients with MacTel type 2 were investigated by fundus reflectometry and two wavelengths fundus autofluorescence (FAF; at 488 nm and 514 nm). Fundus reflectometry showed a reduced MPOD within the central 4 degrees eccentricity that was most absent temporal to the foveola. At 6 degrees, MP density was not different from normative values. Two wavelengths FAF was in accordance with these findings. Fundus reflectometry also allowed separate determination of lutein and zeaxanthin. The patients with MacTel type 2 showed a disproportionally high zeaxanthin reduction. The study suggests that in MacTel type 2, there might be an inability to accumulate MP in the central retina. This disease might serve as a model to further study abnormalities of MP distribution in retinal disorders and to elucidate the mechanisms of MP deposition in the retina.

[Specification of reflectometric measurement complex to evaluate optic density of macular pigments and concentration of phototoxic chemicals in retina].

Suggestion is to specify reflectometric measurement complex based on digital multisensor imaginery fundus-camera, in order to evaluate optic density of macular pigments and concentration of phototoxic chemicals in human retina. The authors presented a review of role played by macular pigments (zeaxanthine and lutein) in human eye viability, analyzed yellow spot as a protective light filter against harmful effects of short-wave light, increasing optic image quality in human eye and responsible for colour vision. Role of evaluating the individual density of macular pigments was stressed as a forecasting efficient criterion of occupational selection in operators performing visual tasks of detection, distance and dimensions measurement for remote objects, monitoring the changeable circumstances.