Carotenoids and Antioxidants in Age-Related Maculopathy Italian Study. Multifocal Electroretinogram Modifications after 1 Year

Fondazione G. B. Bietti-Istituto di Ricovero e Cura a Carattere Scientifico, Roma, Italy.
Ophthalmology (Impact Factor: 6.14). 02/2008; 115(2):324-333.e2. DOI: 10.1016/j.ophtha.2007.05.029
Source: PubMed


To evaluate the influence of short-term carotenoid and antioxidant supplementation on retinal function in nonadvanced age-related macular degeneration (AMD).
Randomized controlled trial.
Twenty-seven patients with nonadvanced AMD and visual acuity > or =0.2 logarithm of the minimum angle of resolution were enrolled and randomly divided into 2 age-similar groups: 15 patients had oral supplementation of vitamin C (180 mg), vitamin E (30 mg), zinc (22.5 mg), copper (1 mg), lutein (10 mg), zeaxanthin (1 mg), and astaxanthin (4 mg) (AZYR SIFI, Catania, Italy) daily for 12 months (treated AMD [T-AMD] group; mean age, 69.4+/-4.31 years; 15 eyes); 12 patients had no dietary supplementation during the same period (nontreated AMD [NT-AMD] group; mean age, 69.7+/-6.23 years; 12 eyes). At baseline, they were compared with 15 age-similar healthy controls.
Multifocal electroretinograms in response to 61 M-stimuli presented to the central 20 degrees of the visual field were assessed in pretreatment (baseline) conditions and, in nonadvanced AMD patients, after 6 and 12 months.
Multifocal electroretinogram response amplitude densities (RAD, nanovolt/deg(2)) of the N1-P1 component of first-order binary kernels measured from 5 retinal eccentricity areas between the fovea and midperiphery: 0 degrees to 2.5 degrees (R1), 2.5 degrees to 5 degrees (R2), 5 degrees to 10 degrees (R3), 10 degrees to 15 degrees (R4), and 15 degrees to 20 degrees (R5).
At baseline, we observed highly significant reductions of N1-P1 RADs of R1 and R2 in T-AMD and NT-AMD patients when compared with healthy controls (1-way analysis of variance P<0.01). N1-P1 RADs of R3-R5 observed in T-AMD and NT-AMD were not significantly different (P>0.05) from controls. No significant differences (P>0.05) were observed in N1-P1 RADs of R1-R5 between T-AMD and NT-AMD at baseline. After 6 and 12 months of treatment, T-AMD eyes showed highly significant increases in N1-P1 RADs of R1 and R2 (P<0.01), whereas no significant (P>0.05) change was observed in N1-P1 RADs of R3-R5. No significant (P>0.05) changes were found in N1-P1 RADs of R1-R5 in NT-AMD eyes.
In nonadvanced AMD eyes, a selective dysfunction in the central retina (0 degrees -5 degrees ) can be improved by the supplementation with carotenoids and antioxidants. No functional changes are present in the more peripheral (5 degrees -20 degrees ) retinal areas.

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Available from: Vincenzo Parisi, Apr 21, 2014
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    • "While in the early stages of AMD visual acuity can be well preserved or only minimally reduced, functional abnormalities involving photoreceptors and/or postreceptoral neurons can be well documented by electrophysiological or psychophysical methods [30-36]. Recently, a randomized clinical trial [37], has demonstrated that dietary supplementation with Saffron is able to improve significantly the focal electroretinogram (fERG) estimated retinal flicker sensitivity in patients with early AMD, suggesting a neuroprotective effect of Saffron on dysfunctional fERG generators, namely photoreceptors, and/or bipolar cells. "
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    ABSTRACT: To determine whether the functional effects of oral supplementation with Saffron, a natural compound that proved to be neuroprotective in early age-related macular degeneration, are influenced by complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) risk genotypes. Thirty-three early AMD patients, screened for CFH (rs1061170) and ARMS2 (rs10490924) polymorphisms and receiving Saffron oral supplementation (20 mg/day) over an average period of treatment of 11 months (range, 6--12), were longitudinally evaluated by clinical examination and focal electroretinogram (fERG)-derived macular (18[degree sign]) flicker sensitivity estimate. fERG amplitude and macular sensitivity, the reciprocal value of the estimated fERG amplitude threshold, were the main outcome measures. After three months of supplementation, mean fERG amplitude and fERG sensitivity improved significantly when compared to baseline values (p < 0.01). These changes were stable throughout the follow-up period. No significant differences in clinical and fERG improvements were observed across different CFH or ARMS2 genotypes. The present results indicate that the functional effect of Saffron supplementation in individual AMD patients is not related to the major risk genotypes of disease.
    Journal of Translational Medicine 09/2013; 11(1):228. DOI:10.1186/1479-5876-11-228 · 3.93 Impact Factor
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    • "Indeed, several in vitro studies have shown that oxidative stress-related RPE cell death and dysfunction was improved when the cells were treated with antioxidants [73], [74], [75], [76]. Furthermore, a significant reduction toward retinal degeneration was reported in clinical trials involving AMD patients ingesting antioxidants such as lutein, zeaxanthin, zinc, vitamin C, and vitamin E [77], [78]. It is likely that the increased levels of DJ-1 in RPE lysates from AMD donors is related to increased oxidative stress in these RPE cells in vivo. "
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    ABSTRACT: DJ-1 is found in many tissues, including the brain, where it has been extensively studied due to its association with Parkinson's disease. DJ-1 functions as a redox-sensitive molecular chaperone and transcription regulator that robustly protects cells from oxidative stress. Retinal pigment epithelial (RPE) cultures were treated with H2O2 for various times followed by biochemical and immunohistological analysis. Cells were transfected with adenoviruses carrying the full-length human DJ-1 cDNA and a mutant construct, which has the cysteine residues at amino acid 46, 53 and 106 mutated to serine (C to S) prior to stress experiments. DJ-1 localization, levels of expression and reactive oxygen species (ROS) generation were also analyzed in cells expressing exogenous DJ-1 under baseline and oxidative stress conditions. The presence of DJ-1 and oxidized DJ-1 was evaluated in human RPE total lysates. The distribution of DJ-1 was assessed in AMD and non-AMD cryosectionss and in isolated human Bruch's membrane (BM)/choroid from AMD eyes. DJ-1 in RPE cells under baseline conditions, displays a diffuse cytoplasmic and nuclear staining. After oxidative challenge, more DJ-1 was associated with mitochondria. Increasing concentrations of H2O2 resulted in a dose-dependent increase in DJ-1. Overexpression of DJ-1 but not the C to S mutant prior to exposure to oxidative stress led to significant decrease in the generation of ROS. DJ-1 and oxDJ-1 intensity of immunoreactivity was significantly higher in the RPE lysates from AMD eyes. More DJ-1 was localized to RPE cells from AMD donors with geographic atrophy and DJ-1 was also present in isolated human BM/choroid from AMD eyes. DJ-1 regulates RPE responses to oxidative stress. Most importantly, increased DJ-1 expression prior to oxidative stress leads to decreased generation of ROS, which will be relevant for future studies of AMD since oxidative stress is a known factor affecting this disease.
    PLoS ONE 07/2013; 8(7):e67983. DOI:10.1371/journal.pone.0067983 · 3.23 Impact Factor
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    • "To our knowledge, this is the first longitudinal study, based on an objective electrophysiological technique, documenting the long-term effects of Saffron antioxidant on retinal function in AMD. While several other studies have already shown significant effects of antioxidant supplementation on retinal function [8] [10] [13], all these previous studies were more limited either in their follow-up duration or in the number of testing sessions. The current data show that changes in fERG threshold (and consequently its reciprocal value sensitivity) after supplementation were within-session consistent, reproducible , and durable over a 15-month follow-up period. "
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    ABSTRACT: Objectives. In a previous randomized clinical trial (Falsini et al. (2010)), it was shown that short-term Saffron supplementation improves retinal flicker sensitivity in early age-related macular degeneration (AMD). The aim of this study was to evaluate whether the observed functional benefits from Saffron supplementation may extend over a longer follow-up duration. Design. Longitudinal, interventional open-label study. Setting. Outpatient ophthalmology setting. Participants. Twenty-nine early AMD patients (age range: 55-85 years) with a baseline visual acuity >0.3. Intervention. Saffron oral supplementation (20 mg/day) over an average period of treatment of 14 (±2) months. Measurements. Clinical examination and focal-electroretinogram-(fERG-) derived macular (18°) flicker sensitivity estimate (Falsini et al. (2010)) every three months over a followup of 14 (±2) months. Retinal sensitivity, the reciprocal value of the estimated fERG amplitude threshold, was the main outcome measure. Results. After three months of supplementation, mean fERG sensitivity improved by 0.3 log units compared to baseline values (P < 0.01), and mean visual acuity improved by two Snellen lines compared to baseline values (0.75 to 0.9, P < 0.01). These changes remained stable over the follow-up period. Conclusion. These results indicate that in early AMD Saffron supplementation induces macular function improvements from baseline that are extended over a long-term followup.
    Evidence-based Complementary and Alternative Medicine 07/2012; 2012:429124. DOI:10.1155/2012/429124 · 1.88 Impact Factor
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