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Diabetic retinopathy is the leading cause of blindness and visual disability globally among working-age adults. Until recently, diabetic eye disease is primarily regarded by its microvasculature complications largely characterized by progressive retinopathy and macular edema. However, a growing body of evidence suggests that hyperglycemia-induced oxidative stress and inflammation play an integral role in the early pathogenesis of diabetic retinopathy by potentiating retinal neurodegeneration. The onset of type 2 diabetes mellitus starts with insulin resistance leading to insulin deficiency, hyperglycemia, and dyslipidemia. Which in turn enhances the pro-oxidant and pro-inflammatory pathways. Additionally, various poor dietary behaviors along with obesity worsen physiological state in diabetics. However, decreased levels and depletion of the endogenous antioxidant defense system in the retina can be sufficiently augmented via carotenoid vitamin therapy. Therefore, dietary supplementation of antioxidant micronutrients particularly macular carotenoids lutein, zeaxanthin and meso-zeaxanthin that promote retinal health and optimal visual performance, may serve as an adjunctive therapy in the management of diabetic eye disease.

Age-related macular degeneration (AMD) remains a leading cause of modifiable vision loss in older adults. Chronic oxidative injury and compromised antioxidant defenses represent essential drivers in the development of retinal neurodegeneration. Overwhelming free radical species formation results in mitochondrial dysfunction, as well as cellular and metabolic imbalance, which becomes exacerbated with increasing age. Thus, the depletion of systemic antioxidant capacity further proliferates oxidative stress in AMD-affected eyes, resulting in loss of photoreceptors, neuroinflammation, and ultimately atrophy within the retinal tissue. The aim of this systematic review is to examine the neuroprotective potential of the xanthophyll carotenoids lutein, zeaxanthin, and meso-zeaxanthin on retinal neurodegeneration for the purpose of adjunctive nutraceutical strategy in the management of AMD. A comprehensive literature review was performed to retrieve 55 eligible publications, using four database searches from PubMed, Embase, Cochrane Library, and the Web of Science. Epidemiology studies indicated an enhanced risk reduction against late AMD with greater dietary consumption of carotenoids, meanwhile greater concentrations in macular pigment demonstrated significant improvements in visual function among AMD patients. Collectively, evidence strongly suggests that carotenoid vitamin therapies offer remarkable synergic protection in the neurosensory retina, with the potential to serve as adjunctive nutraceutical therapy in the management of established AMD, albeit these benefits may vary among different stages of disease.

Digital eye strain is a complex, multifactorial condition that can be caused by excessive screen time exposure to various electronic devices such as smartphones, tablets, e-readers, and computers. Current literature suggests oxidative damage concomitant with a chronic pro-inflammatory state represent significant etiopathogenic mechanisms. The present review aims to discuss the potential dietary role for micronutrients with nutraceutical properties to ameliorate various ocular and vision-related symptoms associated with digital eye strain. For ocular surface dysfunction, enhanced anti-inflammatory benefits with omega-3 polyunsaturated fatty acids have been well documented for treatment of dry eye disease. The anti-oxidative and immunosuppressive properties of anthocyanin phytochemicals may also confer protective effects against visually induced cognitive stress and digital asthenopia. Meanwhile, nutraceutical strategies involving xanthophyll macular carotenoids demonstrate enhanced cognitive functioning and overall visual performance that aids digital eye strain. Collectively, preliminary findings seem to offer a strong line of evidence to substantiate the need for additional randomized controlled trials aimed at treating digital eye strain with adjunctive nutraceutical strategies. Further RCT and comparisons on commercially available nutritional supplements are needed to quantify the clinical benefits.

Primary open-angle glaucoma (POAG) remains a leading cause of irreversible blindness globally. Recent evidence further substantiates sustained oxidative stress, and compromised antioxidant defenses are key drivers in the onset of glaucomatous neurodegeneration. Overwhelming oxidative injury is likely attributed to compounding mitochondrial dysfunction that worsens with age-related processes, causing aberrant formation of free radical species. Thus, a compromised systemic antioxidant capacity exacerbates further oxidative insult in glaucoma, leading to apoptosis, neuroinflammation, and subsequent tissue injury. The purpose of this systematic review is to investigate the neuroprotective benefits of the macular carotenoids lutein, zeaxanthin, and meso-zeaxanthin on glaucomatous neurodegeneration for the purpose of adjunctive nutraceutical treatment in glaucoma. A comprehensive literature search was conducted in three databases (PubMed, Cochrane Library, and Web of Science) and 20 records were identified for screening. Lutein demonstrated enhanced neuroprotection on retinal ganglion cell survival and preserved synaptic activity. In clinical studies, a protective trend was seen with greater dietary consumption of carotenoids and risk of glaucoma, while greater carotenoid levels in macular pigment were largely associated with improved visual performance in glaucomatous eyes. The data suggest that carotenoid vitamin therapy exerts synergic neuroprotective benefits and has the capacity to serve adjunctive therapy in the management of glaucoma.

The macular pigment reflectometer (MPR) objectively measures the overall macular pigment optical density (MPOD) and further provides the lutein optical density (L-OD) and zeaxanthin optical density (Z-OD) in the central 1 degree of the fovea. A modification of the technique was developed to evaluate in vivo carotenoid density eccentric to the fovea. An adjustable track system with red LED lights was placed 6.1 m away from the participant to facilitate ocular fixation. Lights were spaced appropriately to create increments of 1 degree retinal disparity during the reflectometry measurements. All reflectometry measurements were obtained with pupillary dilation. The mean MPR-MPOD value for the central measurement was 0.593 (SD 0.161) with an L-OD to Z-OD ratio of 1:2.61. The MPR-MPOD value at 1 degree was 0.248 and the mean MPR-MPOD value at 2 degrees in the parafoveal region was 0.143. The L-OD to Z-OD ratio at 1 degree and 2 degrees off center was 1.38:1.0 and 2.08:1.0, respectively. The results demonstrate that MPOD measurements obtained using the MPR decrease as a function of retinal eccentricity and that there is a higher concentration of zeaxanthin centrally compared to lutein. The L-OD to Z-OD ratio changes with foveal eccentricity, with twice more lutein than zeaxanthin at 2 degrees off center. Our technique successfully provides a quick in vivo method for the measurement of macular pigment optical density at various foveal eccentricities. The results agree with prior published in vivo and in vitro xanthophyll carotenoid density distribution measurements.

The QuantifEye-Macular Pigment Reflectometer (MPR) is a near commercial prototype that objectively measures lutein, zeaxanthin and overall macular pigment optical density (MPOD). We sought to evaluate the repeatability, intra and inter- observer variability and the effect of pupillary dilation on measurements obtained using the MPR and compare it with the subjective QuantifEye-MPS II, (MPSII). Experiment -1, thirty individuals were examined twice by a clinician. Measurements were performed for 40 seconds each eye and this dataset was parsed into various time intervals example 10-20, 10-30, 10-40 seconds etc. to evaluate the measurements’ repeatability and create clinical protocols that were utilized in the second experiment. Experiment-2 consists of two non-clinicians performing measurements on fifty individuals. Observer-1 performed measurements twice in the selected eye and once in the fellow eye both without and with pupillary dilation. The Observer-2 performed measurement only on the fellow eye both without and with pupillary dilation. Overall the MPR provides MPOD values that are well correlated with the MPSII. Of the various parsing of the data, the data 10-30 interval was the best at obtaining the MPOD, lutein and zeaxanthin values. The lutein and zeaxanthin optical densities were in the ranges of previously published histology results. Dilation was not needed to obtain the MPOD values but provided better lutein and zeaxanthin measurement repeatability. The intra and inter-observer repeatability in experiment-2 was excellent. The current studies have established the clinical protocols to use when measuring MPOD using the MPR and the MPR can provide repeatable and reliable measurements.

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.

Diabetic retinopathy, which was primarily regarded as a microvascular disease, is the leading cause of irreversible blindness worldwide. With obesity at epidemic proportions, diabetes-related ocular problems are exponentially increasing in the developed world. Oxidative stress due to hyperglycemic states and its associated inflammation is one of the pathological mechanisms which leads to depletion of endogenous antioxidants in retina in a diabetic patient. This contributes to a cascade of events that finally leads to retinal neurodegeneration and irreversible vision loss. The xanthophylls lutein and zeaxanthin are known to promote retinal health, improve visual function in retinal diseases such as age-related macular degeneration that has oxidative damage central in its etiopathogenesis. Thus, it can be hypothesized that dietary supplements with xanthophylls that are potent antioxidants may regenerate the compromised antioxidant capacity as a consequence of the diabetic state, therefore ultimately promoting retinal health and visual improvement. We performed a comprehensive literature review of the National Library of Medicine and Web of Science databases, resulting in 341 publications meeting search criteria, of which, 18 were found eligible for inclusion in this review. Lutein and zeaxanthin demonstrated significant protection against capillary cell degeneration and hyperglycemia-induced changes in retinal vasculature. Observational studies indicate that depletion of xanthophyll carotenoids in the macula may represent a novel feature of DR, specifically in patients with type 2 or poorly managed type 1 diabetes. Meanwhile, early interventional trials with dietary carotenoid supplementation show promise in improving their levels in serum and macular pigments concomitant with benefits in visual performance. These findings provide a strong molecular basis and a line of evidence that suggests carotenoid vitamin therapy may offer enhanced neuroprotective effects with therapeutic potential to function as an adjunct nutraceutical strategy for management of diabetic retinopathy.

Purpose: A previous comparative interventional study suggested oral zeaxanthin added to triple therapy of intravitreal bevacizumab, intravitreal corticosteroids and photodynamic therapy with verteporfin for the treatment of neovascular age-related macular degeneration (NVAMD) was comparatively effective and cost-effective. A randomized clinical trial was undertaken to confirm these effects. Methodology: A two-year, triple-blinded, randomized clinical trial enrolled 144 participants (168 eyes) with NVAMD to triple therapy (TT) (intravitreal bevacizumab, reduced-fluence photodynamic therapy and intravitreal dexamethasone) or the same triple therapy with oral zeaxanthin (TTZ) supplementation, 20 mg daily. Data were modeled out to the 11-year life expectancy of the average participant. Results: At 24-months, twenty-seven percent (17/62) of TTZ eyes gained ≥ 15 letters, versus 9% (7/81) of TT eyes (p=0.003). Among unilateral, NVAMD participants, NVAMD developed in 23% (12/53) of TT and 6% (3/47) of TTZ fellow eyes with atrophic age-related macular degeneration (AMD) (p=0.02) by 24 months after baseline. The incremental costutility ratio of oral zeaxanthin supplementation was a remarkably low $30/QALY (quality-adjusted life-year). Zeaxanthin supplementation to TT is cost-effective in every country since the 11-year cost of TTZ ($14,486) exceeds the cost of TT ($14,480) by only $6, yet provides a 0.200 QALY gain. Conclusion: Oral zeaxanthin supplementation of triple therapy for the treatment of neovascular age-related macular degeneration is comparatively effective because it yields improved vision and reduces the incidence of subsequent neovascular age-related macular degeneration in fellow eyes with atrophic age-related macular degeneration by 74%. Oral zeaxanthin supplementation is very cost-effective in the U.S. and worldwide referent to most ophthalmic interventions.

Uveal melanoma cells were inoculated into the choroid of nude mice and treated with or without intraocular injection of zeaxanthin. After 21 days, mice were sacrificed and the eyes enucleated. Histopathological analysis was performed in hematoxylin and eosin stained frozen sections. Melanoma developed rapidly in the control group (without treatment of zeaxanthin). Tumor-bearing eye mass and tumor mass in the control group were significantly greater than those in zeaxanthin treated group. Melanoma in the controlled eyes occupied a large part of the eye, was epithelioid in morphology, and was with numerous mitotic figures. Scleral perforation and extraocular extension were observed in half of the eyes. Melanomas in zeaxanthin treated eyes were significantly smaller with many necrosis and apoptosis areas and no extraocular extension could be found. Quantitative image analysis revealed that the tumor size was reduced by 56% in eyes treated with low dosages of zeaxanthin and 92% in eyes treatment with high dosages of zeaxanthin, as compared to the controls. This study demonstrated that zeaxanthin significantly inhibits the growth and invasion of human uveal melanoma in nude mice, suggesting that zeaxanthin may be a promising agent to be explored for the prevention and treatment of uveal melanoma.

Purpose Oxidative damage and growth factors are implicated in the pathogenesis of retinopathy in diabetes. Recent studies have shown that two dietary carotenoids, lutein and zeaxanthin (Zx), that are specifically concentrated within ocular tissues, may play important roles in maintaining their integrity. This study is to evaluate the potential protective effects of Zx against retinal oxidative damage and growth factors in diabetes. Methods A group of rats received normal powdered diet or powdered diet supplemented with 0.02% or 0.1% Zx soon after induction of diabetes. Age-matched normal rats served as control subjects. At 2 months of diabetes, oxidative stress, vascular endothelial cell growth factor (VEGF), and intercellular adhesion molecule (ICAM)-1 were quantified in the retina. Results Zx supplementation prevented diabetes-induced increase in retinal damage, and increases in VEGF and ICAM-1. The levels of lipid peroxide, oxidatively modified DNA, electron transport complex III, nitrotyrosine, and mitochondrial superoxide dismutase were similar in the retinas of Zx-treated diabetic rats and normal control rats, and these values were significantly different from those obtained from diabetic rats without any supplementation. In the same rats, Zx also prevented diabetes-induced increases in retinal VEGF and ICAM-1. Both 0.02% and 0.1% Zx had similar effects on diabetes-induced retinal abnormalities, and these effects were achieved without ameliorating the severity of hyperglycemia. However, Zx administration failed to prevent a diabetes-induced decrease in retinal GSH levels. Conclusions Zx significantly inhibits diabetes-induced retinal oxidative damage and elevation in VEGF and adhesion molecule, all abnormalities that are associated with the pathogenesis of diabetic retinopathy. The results suggest that Zx supplementation has the potential to inhibit the development of retinopathy in diabetic patients.

Nucleic acids were removed from whole cells and homogenates of Candida utilis by alkaline hydrolysis, enzymatic methods and washing with buffer. True protein of 42% in whole cells became concentrated, ash and carbohydrate contents generally decreased and relative lipid content increased with processing suggesting coprecipitation of lipid-rich membrane material with proteins. The RNA content was 8% in whole cells and 45–97% reductions in RNA were obtained by various methods. Dry weight recoveries ranged from 45–80%. Protein recoveries ranged from 67–98%. Very small changes in amino acid compositions resulted from the various RNA removal methods with 5% or less change in percentage of essential amino acids compared to whole cells. Lysine was 92% available in whole cells and yeast homogenate and in no case did available lysine drop below 88%. Functional properties of the dried preparations, including bulk density, color and taste, protein solubility, water and oil binding, viscosity and heat thickening, foaming capacity and foam stability, and emulsifying capacity, activity and stability were determined and comparative tests were made with functional ingredients from nonyeast sources. Several of the preparations possessed functional properties that were equal or superior to soy flour or whey concentrate.

Candida utilis was grown under controlled conditions and nucleic acids were removed from whole cells and homogenates by alkaline hydrolysis techniques, en-zymatic methods, and washing with buffer. Homogenization released hydrolytic enzymes and proteolytic activity increased with incubation at elevated temperatures under acidic conditions. Slight proteolysis occurred in all incubated samples and this may contribute to protein insolubilization. Very little protein was lost during incu-bation when compared to similar processes using bakers' yeast. This can be due to lower levels of protease activities in C. utilis. Alkaline hydrolysis methods resulted in hydrolysis of some proteins and irreversible insolubilization of the protein. These methods also destroyed any residual enzymatic activities. Heat denaturation studies suggest that protein insolubilization occurs at neutral pH when heat treatments equivalent to or greater than 85° C for 15 min are used. SDS-PAGE methods were used to characterize and monitor changes in protein. Eighteen proteins and/or sub-units were present at levels of 1% or greater. Results may help to explain changesin functional properties of sample preparations which accompany RNA removal.

Purpose Increased oxidative stress and inflammatory mediators are implicated in the development of diabetic retinopathy, and in rats, its development can be prevented by antioxidants. Carotenoids are some of the powerful antioxidants, and diabetes decreases lutein and zeaxanthin levels in the serum and retina. The aim of this study is to investigate the effect of carotenoid containing nutritional supplements (Nutr), which is in clinical trials for ‘Diabetes Vision Function’, on diabetic retinopathy. Methods Streptozotocin-induced diabetic rats (Wistar, male) were fed Purina 5001 supplemented with nutritional supplements containing zeaxanthin, lutein, lipoic acid, omega-3 fatty acids and other nutrients, or without any supplementation. Retinal function was analyzed at ~4 months of diabetes by electroretinography. After 11 months of diabetes, capillary cell apoptosis (TUNEL-staining) and histopathology (degenerative capillaries) were quantified in trypsin-digested retinal vasculature. Retina was also analyzed for mitochondrial damage (by quantifying gene expressions of mtDNA-encoded proteins of the electron transport chain), VEGF and inflammatory mediators, interleukin-1β and NF-k B. Results Diabetes impaired retinal function decreasing the amplitudes of both a- and b-waves. In the same animals, retinal capillary cell apoptosis and degenerative capillaries were increased by 3–4 fold. Gene expressions of mtDNA encoded proteins were decreased, and VEGF, interleukin-1β and NF-k B levels were elevated. Supplementation with the nutrients prevented increased capillary cell apoptosis and vascular pathology, and ameliorated these diabetes-induced retinal abnormalities. Conclusions Nutritional supplementation prevents diabetic retinopathy, and also maintains normal retinal function, mitochondrial homeostasis and inflammatory mediators. Thus, this supplementation could represent an achievable and inexpensive adjunct therapy to also inhibit retinopathy, a slow progressing disease feared most by diabetic patients.