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%

Endurance exercise decreases protein synthesis and ER-mitochondria contacts in mouse skeletal muscle

Exercise is important to maintain skeletal muscle mass through stimulation of protein synthesis, which is a major ATP-consuming process for cells. However, muscle cells have to face high energy demand during contraction. The present study aimed to investigate protein synthesis regulation during aerobic exercise in mouse hindlimb muscles. Male C57Bl/6J mice ran at 12 m/min for 45 min or at 12 m/min for the first 25 min followed by a progressive increase in velocity up to 20 m/min for the last 20 min. Animals were injected intraperitoneally with 40 nmol/g of body weight of puromycin and euthanized by cervical dislocation immediately after exercise cessation. Analysis of gastrocnemius, plantaris, quadriceps, soleus, and tibialis anterior muscles revealed a decrease in protein translation assessed by puromycin incorporation, without significant differences among muscles or running intensities. The reduction of protein synthesis was associated with a marked inhibition of mammalian target of rapamycin complex 1 (mTORC1)-dependent phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1, a mechanism consistent with reduced translation initiation. A slight activation of AMP-activated protein kinase consecutive to the running session was measured but did not correlate with mTORC1 inhibition. More importantly, exercise resulted in a strong upregulation of regulated in development and DNA damage 1 (REDD1) protein and gene expressions, whereas transcriptional regulation of other recognized exercise-induced genes ( IL-6, kruppel-like factor 15, and regulator of calcineurin 1) did not change. Consistently with the recently discovered role of REDD1 on mitochondria-associated membranes, we observed a decrease in mitochondria-endoplasmic reticulum interaction following exercise. Collectively, these data raise questions concerning the role of mitochondria-associated endoplasmic reticulum membrane disruption in the regulation of muscle proteostasis during exercise and, more generally, in cell adaptation to metabolic stress. NEW &amp; NOTEWORTHY How muscles regulate protein synthesis to cope with the energy demand during contraction is poorly documented. Moreover, it is unknown whether protein translation is differentially affected among mouse hindlimb muscles under different physiological exercise modalities. We showed here that 45 min of running decreases puromycin incorporation similarly in 5 different mouse muscles. This decrease was associated with a strong increase in regulated in development and DNA damage 1 protein expression and a significant disruption of the mitochondria and sarcoplasmic reticulum interaction. </jats:p

Dynamic Drusen Remodelling in Participants of the Nutritional AMD Treatment-2 (NAT-2) Randomized Trial.

PURPOSE:To evaluate the dynamic remodeling of drusen in subjects with unilateral neovascular age-related macular degeneration (AMD) receiving a three-year course of oral docosahexaenoic acid (DHA) or placebo. SETTING:Institutional setting. METHODS:Three hundred subjects with age-related maculopathy and neovascular AMD in the fellow eye were randomly assigned to receive either 840 mg/day DHA or placebo for 3 years. Main outcome measures of this post-hoc sub-group analysis were progression of drusen number, total diameter, and total area on fundus photography, and their association with DHA supplementation, socio-demographic and genetic characteristics. RESULTS:Drusen progression was analyzed in 167 subjects that did not develop CNV (87 that received DHA and 80 that received placebo). None of the drusen remodeling outcomes were significantly associated with DHA supplementation. Total drusen diameter reduction in the inner subfield was significantly associated with age (older patients: r = -0.17; p = 0.003). Women showed a tendency to decreased total drusen diameter in the inner subfield with CFH polymorphism (p = 0.03), where women with TT genotype tended to have a greater reduction in drusen diameter than other genotypes (CC and CT). Drusen area in the inner subfield was more reduced in older patients (r = -0.17) and in women (p = 0.01). Drusen number showed no significant trends. CONCLUSIONS:Dynamic drusen remodeling with net reduction in drusen load over three years was found in patients with exudative AMD in one eye and drusen in the other eye (study-eye). This reduction was correlated with increased age and female gender, and showed a tendency to be influenced by CFH genotype, but did not appear to be affected by DHA supplementation. TRIAL REGISTRATION:Controlled-Trials.com ISRCTN98246501

Segmentation of drusen and geographic atrophy (GA).

A) Original red-free fundus photograph B) Original color fundus photograph with areas of drusen and GA outlined (black) C) Color fundus photograph cropped to 6 mm field. D) contrast enhanced color photo. E) segmentation of drusen (green) within the 6 mm field F) areas of GA masked (black).</p

Drusen regression and its correlation with new geographic atrophy (GA).

<p><b>A:</b> Color photo, right eye, Visit 1 (V1). <b>B:</b> V1 photo with soft drusen segmented in green, total pixel area 2,452. GA is not present. <b>C:</b> Color photo, right eye, Visit 5 (V5), showing new GA, <b>D:</b> V5 photo with GAs segmented in blue, total pixel area 4,161. Drusen from V1 that were absorbed in the GA are overlaid and segmented in red, total pixel area 381, or 9% of geographic atrophy total area. Compared to the original drusen area present in V1 of 2,452 pixels, the 381 drusen pixels converting to GA in V5 represent 16% of the original drusen area.</p

Segmentation of reticular pseudodrusen.

<p>A) original fundus photograph with large area containing both reticular macular disease (reticular pseudodrusen) and ordinary soft drusen outlined in black. The soft drusen are confined to the central macula. The reticular pseudodrusen extend to the arcades. B) original color fundus photo C) both reticular pseudodrusen and soft drusen are segmented (green) on the color photo within the area identified in A and within the superimposed Wisconsin grading template. D) The area of reticular macular disease is separately enclosed in red, and was excluded from drusen measurements.</p

Socio-demographic, genetics and drusen characteristics at baseline.

<p>Socio-demographic, genetics and drusen characteristics at baseline.</p

Comparison of drusen characteristics between baseline and 3 years according to treatment group.

<p>Comparison of drusen characteristics between baseline and 3 years according to treatment group.</p

Associations of 3-year drusen number, diameter and area remodeling with socio-demographic and genetics characteristics at baseline.

<p>Associations of 3-year drusen number, diameter and area remodeling with socio-demographic and genetics characteristics at baseline.</p