Ophthalmology

OBJECTIVE: In the current study we aimed to identify metabolites associated with age-related macular degeneration (AMD) by performing the largest metabolome association analysis in AMD to date. In addition, we aimed to determine the effect of AMD-associated genetic variants on metabolite levels, and aimed to investigate associations between the identified metabolites and activity of the complement system, one of the main AMD-associated disease pathways. DESIGN: Case-control assocation analysis of metabolomics data. SUBJECTS: 2,267 AMD cases and 4,266 controls from five European cohorts. METHODS: Metabolomics was performed using a high-throughput H-NMR metabolomics platform, which allows the quantification of 146 metabolite measurements and 79 derivative values. Metabolome-AMD associations were studied using univariate logistic regression analyses. The effect of 52 AMD-associated genetic variants on the identified metabolites was investigated using linear regression. In addition, associations between the identified metabolites and activity of the complement pathway (defined by the C3d/C3 ratio) were investigated using linear regression. MAIN OUTCOME MEASURES: Metabolites associated with AMD RESULTS: We identified 60 metabolites that were significantly associated with AMD, including increased levels of large and extra-large HDL subclasses and decreased levels of VLDL, amino acids and citrate. Out of 52 AMD-associated genetic variants, seven variants were significantly associated with 34 of the identified metabolites. The strongest associations were identified for genetic variants located in or near genes involved in lipid metabolism (ABCA1, CETP, APOE, LIPC) with metabolites belonging to the large and extra-large HDL subclasses. In addition, 57 out of 60 metabolites were significantly associated with complement activation levels, and these associations were independent of AMD status. Increased large and extra-large HDL levels and decreased VLDL and amino acid levels were associated with increased complement activation. CONCLUSIONS: Lipoprotein levels were associated with AMD-associated genetic variants, while decreased essential amino acids may point to nutritional deficiencies in AMD. We observed strong associations between the vast majority of the AMD-associated metabolites and systemic complement activation levels, independent of AMD status. This may indicate biological interactions between the main AMD disease pathways, and suggests that multiple pathways may need to be targeted simultaneously for successful treatment of AMD

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

Growth of Pediococcus acidilactici on sugar cane blackstrap molasses

Pediococcus acidilactici (IL01) has grown in MRS (Man, Rogosa and Sharpe) broth modified by substitution of glucose by 2.0% (MRS-2), 3.0% (MRS-3), 4.0% (MRS-4) and 5.0% (MRS-5) sugar cane blackstrap molasses. The highest acid production was obtained in MRS-5 broth maintained at a constant pH of 5.0. The highest biomass production was obtained when P. acidilactici was grown in MRS-5 broth at initial pH 6.5, while productivity was higher in MRS-2 broth (28.16%). When the MRS-2 broth was utilized at initial pH 6.5 for a 20-hour fermentation period, the highest growth rate (dx/dt) was found in a period of 8 to 16 hours (0.290 g cells/L.h), while the specific growth rate (µ) was 0.175 (h-1) for that period, differently from the 0.441 (h-1) obtained for the period comprising the 4th to the 12th hour. The growth in MRS broth was 5.08% (2.95 g/l) higher than in MRS-2 broth (2.80 g/l). The data obtained have shown that P. acidilactici has had a significant growth in molasses as the main carbon source, and that it is possible to substitute MRS glucose by this carbon source with the purpose of obtaining a more economical growth medium for the potential large scale productions.<br>Pediococcus acidilactici (IL01) cresceu em caldo MRS (Man, Rogosa and Sharpe) modificado por adição de 2,0% (MRS-2), 3,0% (MRS-3), 4,0% (MRS-4) and 5,0% (MRS-5) de melaço de cana de açúcar, em substituição à glicose. A maior produção de ácido ocorreu em caldo MRS-5 com pH constante 5,0. A produção de biomassa foi mais acentuada em caldo MRS-5 com pH inicial de 6,5, embora a produtividade tenha sido maior em caldo MRS-2 (28,16%). Em caldo MRS-2 e em pH inicial de 6,5 durante uma fermentação de 20 horas, a velocidade de crescimento (dx/dt) foi maior entre a 8ª e 16ª hora (0,290 g celulas/L.h) enquanto a velocidade específica de crescimento µ foi 0,175 (h-1) para este período, diferente de 0,441 (h-1) obtido no período compreendido entre a 4ª e 12ª hora. O crescimento em caldo MRS foi 5,08% (2,95 g/l) maior que em caldo MRS-2 (2,80 g/l). Os dados obtidos mostraram que P. acidilactici cresceu bem em melaço como principal fonte de carbono e que é possível substituir a glicose do MRS por esta fonte de carbono, com o objetivo de obter um meio de crescimento mais econômico para eventuais produções em grande escala