zeaxanthin and Diabetic-Retinopathy

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.

Topics: Animals; Antioxidants; Carotenoids; Diabetic Retinopathy; Dietary Supplements; Humans; Lutein; Macular Pigment; Zeaxanthins

Diabetic retinopathy (DR) is one of the most important microvascular complications of diabetes and remains the leading cause of blindness in the working-age individuals. The exact aetiopathogenesis of DR remains elusive despite major advances in basic science and clinical research. Oxidative damage as one of the underlying causes for DR is increasingly being recognised. In humans, three hydroxycarotenoids, lutein (L), zeaxanthin (Z) and

Topics: Animals; Antioxidants; Diabetic Retinopathy; Dietary Supplements; Disease Models, Animal; Humans; Lutein; Macular Degeneration; Neuroprotective Agents; Reactive Oxygen Species; Zeaxanthins

Retinopathy of prematurity (ROP) and diabetic retinopathy (DR) are important causes of blindness among children and working-age adults, respectively. The development of both diseases involves retinal microvascular degeneration, vessel loss and consequent hypoxic and inflammatory pathologic retinal neovascularization. Mechanistic studies have shown that oxidative stress and subsequent derangement of cell signaling are important factors in disease progression. In eye and vision research, role of the dietary xanthophyll carotenoids, lutein and zeaxanthin, has been more extensively studied in adult onset macular degeneration than these other retinopathies. These carotenoids also may decrease severity of ROP in preterm infants and of DR in working-age adults. A randomized controlled clinical trial of carotenoid supplementation in preterm infants indicated that lutein has functional effects in the neonatal eye and is anti-inflammatory. Three multicenter clinical trials all showed a trend of decreased ROP severity in the lutein supplemented group. Prospective studies on patients with non-proliferative DR indicate serum levels of lutein and zeaxanthin are significantly lower in these patients compared to normal subjects. The present review describes recent advances in lutein and zeaxanthin modulation of oxidative stress and inflammation related to ROP and DR and discusses potential roles of lutein/zeaxanthin in preventing or lessening the risks of disease initiation or progression.

Topics: Animals; Diabetic Retinopathy; Humans; Macula Lutea; Retinopathy of Prematurity; Xanthophylls; Zeaxanthins

Macular pigment, composed of lutein, zeaxanthin, and meso-zeaxanthin, is postulated to protect against age-related macular degeneration, likely because of filtering blue light and its antioxidant properties. Macular pigment optical density (MPOD) is reported to be associated with macular function evaluated by visual acuity and multifocal electroretinogram. Given the importance of macular pigment, reliable and accurate measurement methods are important. The main purpose of this study is to determine the reproducibility of MPOD measurement by two-wavelength autofluorescence method using scanning laser ophthalmoscopy.. Sixty-eight eyes of 39 persons were enrolled in the study, including 11 normal eyes, 16 eyes with wet age-related macular degeneration, 16 eyes with dry age-related macular degeneration, 11 eyes with macular edema due to diabetic mellitus, branch retinal vein occlusion or macular telangiectasia, and 14 eyes with tractional maculopathy, including vitreomacular traction, epiretinal membrane, or macular hole. MPOD was measured with a two-wavelength (488 and 514 nm) autofluorescence method with the Spectralis HRA + OCT after pupil dilation. The measurement was repeated for each eye 10 minutes later. The analysis of variance and Bland-Altman plot were used to assess the reproducibility between the two measurements.. The mean MPOD at eccentricities of 1° and 2° was 0.36 ± 0.17 (range: 0.04-0.69) and 0.15 ± 0.08 (range: -0.03 to 0.35) for the first measurement and 0.35 ± 0.17 (range: 0.02-0.68) and 0.15 ± 0.08 (range: -0.01 to 0.33) for the second measurement, respectively. The difference between the 2 measurements was not statistically significant, and the Bland-Altman plot showed 7.4% and 5.9% points outside the 95% limits of agreement, indicating an overall excellent reproducibility. Similarly, there is no significant difference between the first and second measurements of MPOD volume within eccentricities of 1°, 2°, and 6° radius, and the Bland-Altman plot showed 8.8%, 2.9%, and 4.4% points outside the 95% limits of agreement, respectively. The data for the reproducibility did not differ significantly among the various disease and normal eyes.. Under routine examination conditions with pupil dilation, MPOD measurement by two-wavelength autofluorescence method showed a high reproducibility.

Topics: Adult; Aged; Aged, 80 and over; Densitometry; Diabetic Retinopathy; Female; Humans; Lutein; Macular Degeneration; Macular Edema; Macular Pigment; Male; Middle Aged; Optical Imaging; Reproducibility of Results; Zeaxanthins

To evaluate the application of 488 and 514 nm fundus autofluorescence (FAF) and macular pigment optical density (MPOD) imaging in diabetic macular oedema (DMO) and to demonstrate the typical imaging features.. A hundred and twenty-five eyes of 71 consecutive patients with diabetic retinopathy who underwent examination at a specialist university clinic employing a modified Heidelberg Retina Angiograph, using two different light sources of 488 and 514 nm wavelength, were retrospectively reviewed. MPOD images were calculated using modified Heidelberg Eye Explorer software. All images were evaluated by two independent masked graders. Features from FAF and MPOD images were correlated with optical coherence tomography (OCT) imaging findings and inter-grader variability, sensitivity and specificity were calculated using OCT as reference.. Sixty-seven eyes had DMO on OCT. The inter-grader variability was 0.84 for 488 nm FAF, 0.63 for 514 nm FAF and 0.79 for MPOD imaging. Sensitivity and specificity for detection of DMO were 80.6 and 89.7% for 488 nm FAF; 55.2 and 94.8% for 514 nm FAF; and 80.6 and 91.4% for MPOD imaging. In 488 nm FAF and MPOD imaging, DMO was better visualised in comparison with 514 nm FAF imaging, P<0.01. MPOD revealed displacement of macular pigment by intraretinal cysts.. MPOD imaging, and particularly its combination with 488 nm and 514 nm FAF, provides a valuable addition to OCT in the evaluation of DMO and is clinically useful in rapid en-face assessment of the central macula.

Topics: Cross-Sectional Studies; Densitometry; Diabetic Retinopathy; Female; Fluorescein Angiography; Humans; Lutein; Macular Edema; Male; Middle Aged; Observer Variation; Ophthalmoscopy; Retinal Pigments; Retrospective Studies; Sensitivity and Specificity; Tomography, Optical Coherence; Xanthophylls; Zeaxanthins

To compare macular pigment optical density (MPOD) in type 2 diabetic and nondiabetic patients by using dual-wavelength autofluorescence imaging and to investigate the correlation of MPOD with glycosylated hemoglobin (HbA1C) and serum lipid levels.. Forty-three patients were divided into groups 1 (controls, n = 14), 2 (diabetic without retinopathy, n = 17), and 3 (diabetic with mild nonproliferative retinopathy, n = 12). MPOD was measured with a modified confocal scanning laser ophthalmoscope and compared among groups (analysis of variance). The correlation of HbA1C and serum lipid (HDL, LDL, total cholesterol, and triglycerides) levels with MPOD was determined for each group (linear regression analysis).. Mean ± SD ages in groups 1 (56.2 ± 11.7 years), 2 (58.6 ± 11.5 years), and 3 (62.8 ± 9.8 years) were similar (P = 0.324). Mean MPOD averaged in a 2°-diameter circle around the fovea was significantly different between the three groups: 1, (0.29 ± 0.07 density units [DU]), 2 (0.22 ± 0.09 DU), and 3 (0.14 ± 0.05 DU) (P < 0.001). There was a significant difference in mean MPOD levels at 0.5° between groups 1 (0.51 ± 0.12 DU) and 2 (0.24 ± 0.11 DU; P < 0.001), but not between groups 2 and 3 (0.33 ± 0.15 DU; P > 0.05). A significant inverse correlation was observed between HbA1C levels and mean MPOD, averaged at 2° around the fovea in all patients (r = -0.63, P < 0.001). No significant correlations were found between MPOD and serum lipid levels or age.. Type 2 diabetic patients, with or without retinopathy, had reduced MPOD when compared with that in nondiabetic patients. In addition, a significant inverse correlation between MPOD and HbA1C levels was observed.

Topics: Densitometry; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Fluorescein Angiography; Glycated Hemoglobin; Humans; Image Enhancement; Lipids; Lutein; Male; Middle Aged; Ophthalmoscopy; Prospective Studies; Retina; Retinal Pigments; Xanthophylls; Zeaxanthins

Diabetic retinopathy increases with duration of diabetes and may be associated with carotenoid status. Carotenoids alter the pro-oxidation/antioxidation balance, and circulating levels depend largely on dietary intake. Lower levels have been reported in diabetes and age-related macular degeneration; however, little is known of the relationship between carotenoids and diabetic complications. Consequently, the purpose of the present study was to evaluate the relationship between plasma carotenoids and diabetic retinopathy. We assessed the carotenoid-retinopathy relationship in 111 individuals with type 2 diabetes in a community-based, cross-sectional study. We photodocumented retinal status and used HPLC to measure plasma carotenoid concentrations. Data for clinical and demographic variables and risk factors for diabetic retinopathy were obtained from 24 h urine and fasting blood samples, and an interviewer-assisted lifestyle questionnaire. We found that the combined lycopene and lutein/zeaxanthin (non-pro-vitamin A (non-PVA) carotenoid) concentration when compared with the pro-vitamin A (PVA) carotenoids (alpha-carotene, beta-carotene and beta-cryptoxanthin) was significantly lower in the retinopathy than non-retinopathy group (OR 1.2 (95% CI 1.0, 1.4) v. 1.6 (95% CI 1.4, 1.7), respectively; P=0.009). A higher non-PVA:PVA ratio also predicted a lower risk of diabetic retinopathy, after adjustment for potential confounders (OR 0.33 (95% CI 0.12, 0.95); P=0.039). Finally, a higher concentration of PVA carotenoids was associated with greater odds of diabetic retinopathy, after adjustment for risk factors (P=0.049). We suggest synergies between carotenoids are implicated in diabetic retinopathy, independent of established risk factors. Importantly, our observations indicate dietary modulation of retinopathy risk may be possible by increasing intakes of lutein- and lycopene-rich foods.

Topics: Adult; Aged; Antioxidants; beta Carotene; Biomarkers; Blood Glucose; Carotenoids; Chi-Square Distribution; Cross-Sectional Studies; Cryptoxanthins; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Lutein; Lycopene; Male; Middle Aged; Risk; Xanthophylls; Zeaxanthins

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.. 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.. 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.. 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.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Deoxyguanosine; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Diet; Electron Transport Complex III; Intercellular Adhesion Molecule-1; Male; Nitric Oxide Synthase Type II; Oxidative Stress; Rats; Rats, Inbred Lew; RNA, Messenger; Superoxide Dismutase; Tyrosine; Vascular Endothelial Growth Factor A; Xanthophylls; Zeaxanthins