Molecular basis of cobalamin-dependent RNA modification

Queuosine (Q) was discovered in the wobble position of a transfer RNA (tRNA) 47 years ago, yet the final biosynthetic enzyme responsible for Q-maturation, epoxyqueuosine (oQ) reductase (QueG), was only recently identified. QueG is a cobalamin (Cbl)-dependent, [4Fe-4S] cluster-containing protein that produces the hypermodified nucleoside Q in situ on four tRNAs. To understand how QueG is able to perform epoxide reduction, an unprecedented reaction for a Cbl-dependent enzyme, we have determined a series of high resolution structures of QueG from Bacillus subtilis. Our structure of QueG bound to a tRNA[superscript Tyr] anticodon stem loop shows how this enzyme uses a HEAT-like domain to recognize the appropriate anticodons and position the hypermodified nucleoside into the enzyme active site. We find Q bound directly above the Cbl, consistent with a reaction mechanism that involves the formation of a covalent Cbl-tRNA intermediate. Using protein film electrochemistry, we show that two [4Fe-4S] clusters adjacent to the Cbl have redox potentials in the range expected for Cbl reduction, suggesting how Cbl can be activated for nucleophilic attack on oQ. Together, these structural and electrochemical data inform our understanding of Cbl dependent nucleic acid modification.National Science Foundation (U.S.) (MCB 1122977)National Institutes of Health (U.S.) (GM72623 S01, GM120283, and GM17151

Methanol poisoning: two case studies of blindness in Indonesia

We report two recent cases of methanol intoxication in French patients living in Bali. These intoxications were secondary to the consumption of adulterated liquor. Both patients presented acute bilateral loss of vision a few days after methanol ingestion with no sign of recovery. The fundus showed bilateral optic atrophy that was well correlated with retinal nerve fibre layer thickness measured with spectral-domain optical coherence tomography and compatible with toxic optic neuropathy. In one of the patients, macular swelling in one eye was observed. Electroretinograms were normal contrasting with abolished visual evoked potentials. Methanol was isolated from a sample of the beverage with gas chromatography. Methanol intoxication may occur in Asia and therefore adequate information for tourists and the local population is required

Maintenance of anticoagulant and antiplatelet agents for patients undergoing peribulbar anesthesia and vitreoretinal surgery

PURPOSE: : To establish the prevalence of anticoagulation (vitamin K antagonists) and antiplatelet agent therapy in patients undergoing vitreoretinal surgery and to compare the outcome of peribulbar anesthesia and vitreoretinal surgery between users and nonusers. METHODS: : We conducted a retrospective case series study in one academic center. No changes in the treatment regimen were made before surgery. Patients were divided into 3 groups: G1, patients with no anticoagulant or antiplatelet therapy; G2, patients treated with anticoagulants; and G3, patients treated with aspirin, clopidogrel, or both. RESULTS: : Two hundred and six eyes (206 patients) were included. G1, 144 eyes (69.9%) without any anticoagulant or antiplatelet therapy (69.9%); G2, 12 eyes (5.8%) with anticoagulants; and G3, 44 eyes (21.4%) with antiplatelet agents. Six patients (6 eyes) (2.9%) received both anticoagulant and antiplatelet agents. The incidence of overall and mild postoperative hemorrhagic complications was similar between groups, P = 0.075 and P = 0.127, respectively. However, potential sight-threatening hemorrhagic complications were more frequent in patients receiving antiplatelet agents, P < 0.003. CONCLUSION: : Peribulbar anesthesia for vitreoretinal surgery can probably be performed safely in patients receiving anticoagulants. However, retinal surgeons should be aware that severe bleeding complications are more frequent in patients receiving antiplatelet therapy

Normal values for fundus perimetry with the MAIA microperimeter and short-term repeatability evaluation

National audiencePurpose To assess retinal sensitivity by means of microperimetry and to evaluate the intersession fluctuation using the MAIA microperimeter in healthy volunteers. Methods Prospective, monocentre study. Fifty‐six healthy volunteers (age range, 20–80 years), underwent an automatic, full‐threshold microperimetry of the central field (custom grid, area of 10° in diameter, 37 stimulated points), with the MAIA microperimeter (CenterVue, Padova, Italy). A subgroup of 24 subjects was retested after 1 h (test 2) and 1 week (test 3) to determine the repeatability of the technique. A subgroup of 22 subjects was also tested on the OPKO microperimeter (Optos, Dunfermline, Scotland) (area of 10° in diameter, 28 stimulated points). Results Median age was 30 years [25.3–47.8]. The overall mean sensitivity for test 1 was 29.4 ± 1.4 dB, 29.8 ± 1.0 dB for test 2 and 29.9 ± 1.1 dB for test 3, respectively. Linear regression analysis showed a significant 0.5 dB sensitivity loss for each decade of life (r² = 0.27). In a subset of 24 subjects, the repeatability of the test performed at 3 separate visits showed a statistically significant difference between test 1 and 3 (p < 0.004). Test 2 and 3 showed consistent values over time (p = 0.160). Furthermore, the MAIA showed higher threshold values than the OPKO for all test locations. Linear regression of the perimetric results showed significant correlation between the 2 machines (r = 0.44; p < 0.001). Conclusions This study found an age‐related macular sensitivity loss. These findings are in agreement with previous data obtained with the MP1 and the OPKO microperimeters. The increase in sensitivity between test 1 and test 2 and 3 should be taken into account in clinical practice. Automatic fundus perimetry with the MAIA microperimeter allows for accurate, repeatable examination, if a training session is performed

Effect of an adjunctive first-line intravitreal betamethasone injection in postoperative endophthalmitis

International audienc

Vue d'ensemble des pratiques médicales dans la DMLA exsudative en France

Wet AMD is characterized by the formation of choroidal neovascularization, mediated by vascular endothelial growth factor (VEGF) and responsible for a decrease in visual acuity and metamorphopsia of sudden onset. Intravitreal anti-VEGF can stabilize or even improve visual acuity. Although there is a consensus among ophthalmologists about the induction phase injection of anti-VEGF, there appear to be differences in practice regarding therapeutic treatment modalities. The goal of this work was to explore this hypothesis and to better understand real life practices

Erythrocyte fatty acid composition of controls and diabetic patients without or with diabetic retinopathy at mild, moderate, severe, and proliferative stages (% of total fatty acid methyl esters (FAMEs) + dimethylacetals (DMAs)).

a<p>Based on Kruskall-Wallis test, significantly different when compared to controls (<i>P</i><0.05).</p><p>Erythrocyte fatty acid composition of controls and diabetic patients without or with diabetic retinopathy at mild, moderate, severe, and proliferative stages (% of total fatty acid methyl esters (FAMEs) + dimethylacetals (DMAs)).</p

Red blood cell membrane levels of docosahexaenoic acid (DHA), total n-3 PUFA, n-6 PUFA, and total n-6 PUFA/total n-3 PUFA in control subjects and diabetic patients with or without DR.

<p>Results are expressed as means ± SEM. * based on Kruskall-Wallis test (<i>P</i><0.05).</p

Concentration of individual species of phosphatidyl-choline (PC) and plasmenyl-choline (PlsC) in erythrocytes from controls and diabetic patients without or with mild, moderate, severe or proliferative diabetic retinopathy (results are expressed as µg of mg phospholipids).

<p>Abbreviations of individual PC and PlsC species are as follows: position on the glycerol backbone as shown as sn-1/sn-2 of the fatty acid and fatty alcohol radicals (abbreviated as number of carbons: number of double bonds).</p>a<p>Based on Kruskall-Wallis test, significantly different when compared to controls (<i>P</i><0.05).</p><p>Concentration of individual species of phosphatidyl-choline (PC) and plasmenyl-choline (PlsC) in erythrocytes from controls and diabetic patients without or with mild, moderate, severe or proliferative diabetic retinopathy (results are expressed as µg of mg phospholipids).</p