Predicting the retinal content in omega-3 fatty acids for age-related macular-degeneration.
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ABSTRACT:
SUBMITTER: Acar N
PROVIDER: S-EPMC8243522 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
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Predicting the retinal content in omega-3 fatty acids for age-related macular-degeneration.
Acar Niyazi N Merle Bénédicte M J BMJ Ajana Soufiane S He Zhiguo Z Grégoire Stéphane S Hejblum Boris P BP Martine Lucy L Buaud Benjamin B Bron Alain M AM Creuzot-Garcher Catherine P CP Korobelnik Jean-François JF Berdeaux Olivier O Jacqmin-Gadda Hélène H Bretillon Lionel L Delcourt Cécile C
Clinical and translational medicine 20210701 7
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Project description:BackgroundEvidence from animal models and observational studies in humans has suggested that there is an inverse relationship between dietary intake of omega 3 long-chain polyunsaturated fatty acids (LCPUFA) and risk of developing age-related macular degeneration (AMD) or progression to advanced AMD.ObjectivesTo review the evidence that increasing the levels of omega 3 LCPUFA in the diet (either by eating more foods rich in omega 3 or by taking nutritional supplements) prevents AMD or slows the progression of AMD.Search methodsWe searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2015), EMBASE (January 1980 to February 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to February 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 2 February 2015.Selection criteriaWe included randomised controlled trials (RCTs) where increased dietary intake of omega 3 LCPUFA was compared to placebo or no intervention with the aim of preventing the development of AMD, or slowing its progression.Data collection and analysisBoth authors independently selected studies, assessed them for risk of bias and extracted data. One author entered data into RevMan 5 and the other author checked the data entry. We conducted a meta-analysis for one primary outcome, progression of AMD, using a fixed-effect inverse variance model.Main resultsWe included two RCTs in this review, in which 2343 participants with AMD were randomised to receive either omega 3 fatty acid supplements or a placebo. The trials, which had a low risk of bias, were conducted in the USA and France. Overall, there was no evidence that people who took omega 3 fatty acid supplements were at decreased (or increased risk) of progression to advanced AMD (pooled hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.84 to 1.10, high quality evidence). Similarly, people taking these supplements were no more (or less) likely to lose 15 or more letters of visual acuity (USA study HR 0.96, 95% CI 0.84 to 1.10; French study at 36 months risk ratio (RR) 1.25, 95% CI 0.69 to 2.26, participants = 230). The number of adverse events was similar in the intervention and placebo groups (USA study participants with one or more serious adverse event RR 1.00, 95% CI 0.91 to 1.09, participants = 2080; French study total adverse events RR 1.05, 95% CI 0.97 to 1.13, participants = 263).Authors' conclusionsThis review found that omega 3 LCPUFA supplementation in people with AMD for periods up to five years does not reduce the risk of progression to advanced AMD or the development of moderate to severe visual loss. No published randomised trials were identified on dietary omega 3 fatty acids for primary prevention of AMD. Currently available evidence does not support increasing dietary intake of omega 3 LCPUFA for the explicit purpose of preventing or slowing the progression of AMD.
| S-EPMC7087473 | biostudies-literature
Project description:PurposeTo examine the association between omega-3 polyunsaturated fatty acids, docosahexaenoic acid, and eicosapentaenoic acid and age-related macular degeneration (AMD) in the Multi-Ethnic Study of Atherosclerosis cohort.MethodsMulti-Ethnic Study of Atherosclerosis is a multicenter, prospective cohort study designed to identify risk factors for cardiovascular disease in four ethnic groups. Six thousand eight hundred and fourteen participants of White, African American, Hispanic/Latino, and Chinese descent, aged 45-84 years, were recruited, with those found to have cardiovascular disease excluded. Our study population included all Multi-Ethnic Study of Atherosclerosis participants with baseline polyunsaturated fatty acid measurements and retinal photography at Examination 5 (n = 3,772). Fundus photographs were assessed for AMD using a standard grading protocol. Relative risk regression (log link) determined associations between polyunsaturated fatty acid levels and AMD.ResultsThere was a significant association between increasing docosahexaenoic acid levels and increasing docosahexaenoic acid + eicosapentaenoic acid levels with reduced risk for early AMD (n = 214 participants with early AMD, of which n = 99 (46.3%) are non-White). Eicosapentaenoic acid levels alone were not significantly associated with AMD.ConclusionOur analysis suggests increasing levels of docosahexaenoic acid are associated with reduced risk for early AMD in a multiethnic cohort. This represents the first racially diverse study demonstrating an association between omega-3 polyunsaturated fatty acids and AMD risk.
| S-EPMC9232932 | biostudies-literature
Project description:To identify disease-specific transcriptional programs in retinal pigment epithelium (RPE) cells, fibroblasts from 43 patients with geographic atrophy (GA) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated into RPE and compared to those from 36 healthy individuals. 127,659 RPE cells were profiled via single cell RNA-sequencing (scRNA-seq) and cell classification identified 7 cellular states related to RPE maturation.
2022-06-20 | E-MTAB-11642 | biostudies-arrayexpress
Project description:BackgroundLong-chain polyunsaturated fatty acids of the omega-6 and omega-3 families affect processes implicated in vascular and neural retinal disease pathogenesis. This study aimed to investigate the association between the dietary omega-6 to omega-3 fatty acid ratio and age-related macular degeneration (AMD).MethodsWe conducted a cross-sectional analysis using a nationwide representative sample of older adults (≥ 50 years), including 1,944 men and 2,592 women, from the Korea National Health and Nutrition Examination Survey (2017-2018). Omega-6 and omega-3 fatty acid intakes were collected through a 24-hour recall method and used to calculate the omega-6 to omega-3 fatty acid ratio. Associations between the ratio and AMD were determined using odds ratios (ORs) from multivariate logistic regressions.ResultsThe prevalence of AMD was 19.8% and 17.7% in Korean men and women, respectively. In women, the multivariable-adjusted OR for incurring AMD was significantly higher in the 2nd (OR = 1.36; 95% CI = 1.02-1.81) and 3rd (OR = 1.36; 95% CI = 1.02-1.83) tertiles of the dietary omega-6 to omega-3 fatty acid ratio than in the 1st tertile (OR = 1, the reference OR) (P = 0.036 for this trend). However, this association was not observed in men.ConclusionsThese results suggest that high omega-6 to omega-3 fatty acid ratios may be associated with an increased prevalence of AMD among Korean women.
| S-EPMC11892259 | biostudies-literature
Project description:Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, we compared omega-3 (n-3) fatty acid with DHA (22:6) and omega-6 (n-6) fatty acid with arachidonic acid (AA; 20:4) pathways. n-3 PC(22:6/22:6, 44:12) and n-6 PC(20:4/20:4, 40:8) showed differences among male/female, macula/periphery, and normal/AMD retinas. Periphery of AMD retina males increased 44:12 abundance, while normal females increased 40:8 (all macula had an upward 40:8 tendency). We also showed that female AMD switched from n-3 to n-6 fatty acids; most changes in AMD occurred in the periphery of female AMD retinas. DHA and VLC-PUFA release from PCs leads to conversion in pro-survival NPD1 and ELVs. The loss of the neuroprotective precursors of ELVs in the retina periphery from AMD facilitates uncompensated stress and cell loss. In AMD, the female retina loses peripheral rods VLC-PUFAs to about 33% less than in males limiting ELV formation and its protective bioactivity.
| S-EPMC11371070 | biostudies-literature
Project description:ImportanceAfter the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up.ObjectiveTo assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD).Design, setting, and participantsThis was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022.InterventionsDuring the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively.Main outcomes and measuresSelf-reported lung cancer and late AMD validated with medical records.ResultsThis study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P = .91). When the lutein/zeaxanthin main effects analysis was restricted to those randomly assigned to beta carotene, the HR was 0.80 (95% CI, 0.68-0.92; P = .002). A direct analysis of lutein/zeaxanthin vs beta carotene showed the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02). The HR for low vs high zinc was 1.04 (95% CI, 0.94-1.14; P = .49), and the HR for no beta carotene vs beta carotene was 1.04 (95% CI, 0.94-1.15; P = .48).Conclusions and relevanceResults of this long-term epidemiologic follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.
| S-EPMC9164119 | biostudies-literature
Project description:PurposeEvaluate the relationship between retinal vascular caliber and age-related macular degeneration (AMD) severity or progression.MethodsA retrospective secondary analysis of 1172 fundus photographs and clinical data from the prospective Age-Related Eye Disease Study (AREDS). Central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) were measured using the Parr-Hubbard-Knudtson formula. Univariate and multivariate regressions were used to determine the association of CRAE, CRVE, and AVR with age, sex, smoking status, presence of cilioretinal artery, and AMD severity at baseline and 5 years using the 9-step AMD severity score.ResultsOnly CRAE and CRVE were higher in men (P < 0.001), current smokers (P < 0.001), and the eyes with a cilioretinal artery (P=0.009 - 0.043). AMD severity was greater in older patients (P=0.001), current smokers (P=0.012), the eyes without a cilioretinal artery (P=0.001), and lower AVR (P=0.034) on multivariate regression but was not influenced by CRAE or CRVE (P=0.240 - 0.500). Choroidal neovascularization (CNV) presence was associated with older age (P=0.003) and absence of a cilioretinal artery (P=0.009), while central geographic atrophy (CGA) was associated with narrower CRAE (P=0.002) and possibly AVR (P=0.046). None of the retinal vessel parameters were predictive of AMD severity score or new onset of CNV or CGA at 5 years.ConclusionA lower arteriole-to-venule ratio may be associated with AMD severity, with narrower arterioles seen in the eyes with geographic atrophy, suggesting a role of the retinal vasculature in AMD pathophysiology. This trial is registered with ClinicalTrials.gov Identifier: NCT00000145.
| S-EPMC9357695 | biostudies-literature
Project description:Induced pluripotent stem cells generated from patients with geographic atrophy as well as healthy individuals were differentiated to retinal pigment epithelium (RPE) cells. By integrating transcriptional profiles of 127,659 RPE cells generated from 43 individuals with geographic atrophy and 36 controls with genotype data, we identified 439 expression Quantitative Trait (eQTL) loci in cis that were associated with disease status and specific to subpopulations of RPE cells. We identified loci linked to two genes with known associations with geographic atrophy - PILRB and PRPH2, in addition to 43 genes with significant genotype x disease interactions that are candidates for novel genetic associations for geographic atrophy. On a transcriptome-only level, we identified molecular pathways significantly upregulated in geographic atrophy-RPE including in mitochondrial functions, metabolic pathways, and extracellular cellular matrix reorganisation. We subsequently implemented a large-scale proteomics analysis, confirming modification in proteins associated with these pathways. We also identified six significant protein (p) QTL that regulate protein expression in the RPE cells and in geographic atrophy - two of which share variants with cis-eQTL, including proteins involve in mitochondrial biology and neuodegeneration. Investigation of mitochondrial functions in the two cohorts confirmed a modification of respiration etc…. This study provides strong proof of concept of the validity of using iPSC for the modeling of complex diseases. It is the first to use a large scale patient -derived iPSC cohort to uncover important differences in RPE homeostasis associated with geographic atrophy. It clearly identifies mitochondrial activity as a core constitutive difference of the RPE from patients with geographic atrophy, and could be a target of potential therapies for this condition (STACEY/MATT).
2022-06-01 | PXD029501 | Pride
Project description:ObjectivesTo assess a recently described CNN (convolutional neural network) DARC (Detection of Apoptosing Retinal Cells) algorithm in predicting new Subretinal Fluid (SRF) formation in Age-related-Macular-Degeneration (AMD).MethodsAnonymized DARC, baseline and serial OCT images (n = 427) from 29 AMD eyes of Phase 2 clinical trial (ISRCTN10751859) were assessed with CNN algorithms, enabling the location of each DARC spot on corresponding OCT slices (n = 20,629). Assessment of DARC in a rabbit model of angiogenesis was performed in parallel.ResultsA CNN DARC count >5 at baseline was significantly (p = 0.0156) related to development of new SRF throughout 36 months. Prediction rate of eyes using unique DARC spots overlying new SRF had positive predictive values, sensitivities and specificities >70%, with DARC count significantly (p < 0.005) related to the magnitude of SRF accumulation at all time points. DARC identified earliest stages of angiogenesis in-vivo.ConclusionsDARC was able to predict new wet-AMD activity. Using only an OCT-CNN definition of new SRF, we demonstrate that DARC can identify early endothelial neovascular activity, as confirmed by rabbit studies. Although larger validation studies are required, this shows the potential of DARC as a biomarker of wet AMD, and potentially saving vision-loss.
| S-EPMC8011474 | biostudies-literature
Project description:PurposeAspirin and omega-3 fatty acids (FAs) are potential disease modifiers of age-related macular degeneration (AMD), but previous studies have produced inconsistent findings. Randomised evidence for the efficacy and safety of aspirin and omega-3 FAs on AMD is presented in this study.DesignASCEND-Eye is a substudy of eye effects in the 2×2 factorial design ASCEND (A Study of Cardiovascular Events iN Diabetes) double-blind, randomised, placebo-controlled trial for the primary prevention of cardiovascular events. Reports of AMD diagnoses were sourced from 6 monthly ASCEND follow-up questionnaires and a Visual Function Questionnaire.Participants15 480 UK adults at least 40 years of age with diabetes but no evident cardiovascular disease.Interventions100 mg aspirin daily versus placebo and, separately, 1 g omega-3 FAs daily versus placebo.Main outcome measureThe first post-randomisation reports of AMD.ResultsDuring 7.4 years of follow-up, 122 (1.6%) participants randomised to aspirin were reported as having AMD, compared with 138 (1.8%) randomised to placebo (rate ratio 0.88; 95% CI 0.69 to 1.12; p=0.31). AMD occurred in 130 (1.7%) participants randomised to omega-3 FAs, compared with 130 (1.7%) randomised to placebo (rate ratio 0.99; 95% CI 0.78 to 1.27; p=0.99).ConclusionNo clinically-meaningful effects of aspirin or omega-3 FAs on AMD were found. Although the study had very limited statistical power to detect clinically relevant effects, these data overcome some methodological limitations of previous observational studies, providing randomised evidence of both treatments on AMD, which could contribute to future meta-analyses.Trial registration numberISRCTN60635500 and NCT00135226.
| S-EPMC11865773 | biostudies-literature