Vitreous inflammatory factors and serous retinal detachment in central retinal vein occlusion: a case control series

<p>Abstract</p> <p>Background</p> <p>This study investigated whether the vitreous fluid levels of soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), pigment epithelium-derived factor (PEDF), and soluble intercellular adhesion molecule 1 (sICAM-1) were associated with the occurrence of serous retinal detachment (SRD) in patients with central retinal vein occlusion (CRVO).</p> <p>Methods</p> <p>We recruited 33 patients with CRVO and macular edema, as well as 18 controls with nonischemic ocular diseases. Eighteen of the 33 patients with CRVO showed SRD on optical coherence tomography of the macula (defined as subretinal accumulation of fluid with low reflectivity), while the other 15 patients only had cystoid macular edema (CME, defined as hyporeflective intraretinal cavities). Retinal ischemia was evaluated by measuring the area of capillary non-perfusion using fluorescein angiography and the public domain Scion Image program, while central macular thickness (CMT) was examined by optical coherence tomography. Vitreous fluid samples were obtained during pars plana vitrectomy and levels of the target molecules were measured by enzyme-linked immunosorbent assay.</p> <p>Results</p> <p>Ischemia was significantly more common in the SRD group (17/18 patients) than in the CME group (5/15 patients) (<it>P </it>< 0.001). The vitreous fluid level of sICAM-1 increased significantly across the three groups from the control group (4.98 ± 1.73 ng/ml) to the CME group (15.4 ± 10.1 ng/ml) and the SRD group (27.1 ± 17.7 ng/ml) (<it>p_trend</it>< 0.001). The vitreous fluid level of sVEGFR-2 also showed a significant increase across the three groups (1083 ± 541 pg/ml, 1181 ± 522 pg/ml, and 1535 ± 617 pg/ml, respectively, <it>p_trend</it>= 0.019). On the other hand, the vitreous fluid level of PEDF showed a significant decrease across the three groups (56.4 ± 40.0 ng/ml, 24.3 ± 17.3 ng/ml, and 16.4 ± 12.6 ng/ml, respectively, <it>p_trend</it>< 0.001).</p> <p>Conclusions</p> <p>Higher levels of inflammatory factors (sICAM-1 and sVEGFR-2) and lower levels of anti-inflammatory PEDF were observed in macular edema patients with SRD, suggesting that inflammation plays a key role in determining the severity of CRVO.</p

Optimal waist circumference cut-off points and ability of different metabolic syndrome criteria for predicting diabetes in Japanese men and women: Japan Epidemiology Collaboration on Occupational Health Study

Abstract Background We sought to establish the optimal waist circumference (WC) cut-off point for predicting diabetes mellitus (DM) and to compare the predictive ability of the metabolic syndrome (MetS) criteria of the Joint Interim Statement (JIS) and the Japanese Committee of the Criteria for MetS (JCCMS) for DM in Japanese. Methods Participants of the Japan Epidemiology Collaboration on Occupational Health Study, who were aged 20–69 years and free of DM at baseline (n = 54,980), were followed-up for a maximum of 6 years. Time-dependent receiver operating characteristic analysis was used to determine the optimal cut-off points of WC for predicting DM. Time-dependent sensitivity, specificity, and positive and negative predictive values for the prediction of DM were compared between the JIS and JCCMS MetS criteria. Results During 234,926 person-years of follow-up, 3180 individuals developed DM. Receiver operating characteristic analysis suggested that the most suitable cut-off point of WC for predicting incident DM was 85 cm for men and 80 cm for women. MetS was associated with 3–4 times increased hazard for developing DM in men and 7–9 times in women. Of the MetS criteria tested, the JIS criteria using our proposed WC cut-off points (85 cm for men and 80 cm for women) had the highest sensitivity (54.5 % for men and 43.5 % for women) for predicting DM. The sensitivity and specificity of the JCCMS MetS criteria were ~37.7 and 98.9 %, respectively. Conclusion Data from the present large cohort of workers suggest that WC cut-offs of 85 cm for men and 80 cm for women may be appropriate for predicting DM for Japanese. The JIS criteria can detect more people who later develop DM than does the JCCMS criteria

Visual acuity and foveal thickness after vitrectomy for macular edema associated with branch retinal vein occlusion: a case series

Abstract Background The mechanism by which vitrectomy improves macular edema in patients with branch retinal vein occlusion remains unclear, although intraocular levels of vascular endothelial growth factor have been suggested to influence the visual prognosis and macular edema. Methods A series of 54 consecutive patients (54 eyes) with branch retinal vein occlusion was studied prospectively. All patients underwent pars plana vitrectomy for treatment of macular edema. Best corrected visual acuity and retinal thickness (examined by optical coherence tomography) were assessed before and after surgery. The level of vascular endothelial growth factor in vitreous fluid harvested at operation was determined. Patients were followed for at least 6 months postoperatively. Results Both the visual acuity and the retinal thickness showed significant improvement at 6 months postoperatively (P = 0.0002 and P Conclusions These results suggest that the vitreous level of vascular endothelial growth factor might influence the visual prognosis and the response of macular edema to vitrectomy in patients with branch retinal vein occlusion.</p

Current status of space gravitational wave antenna DECIGO and B-DECIGO

Deci-hertz Interferometer Gravitational Wave Observatory (DECIGO) is the future Japanese space mission with a frequency band of 0.1 Hz to 10 Hz. DECIGO aims at the detection of primordial gravitational waves, which could be produced during the inflationary period right after the birth of the universe. There are many other scientific objectives of DECIGO, including the direct measurement of the acceleration of the expansion of the universe, and reliable and accurate predictions of the timing and locations of neutron star/black hole binary coalescences. DECIGO consists of four clusters of observatories placed in the heliocentric orbit. Each cluster consists of three spacecraft, which form three Fabry-Perot Michelson interferometers with an arm length of 1,000 km. Three clusters of DECIGO will be placed far from each other, and the fourth cluster will be placed in the same position as one of the three clusters to obtain the correlation signals for the detection of the primordial gravitational waves. We plan to launch B-DECIGO, which is a scientific pathfinder of DECIGO, before DECIGO in the 2030s to demonstrate the technologies required for DECIGO, as well as to obtain fruitful scientific results to further expand the multi-messenger astronomy.Comment: 10 pages, 3 figure

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Current status of space gravitational wave antenna DECIGO and B-DECIGO

The Deci-hertz Interferometer Gravitational Wave Observatory (DECIGO) is a future Japanese space mission with a frequency band of 0.1 Hz to 10 Hz. DECIGO aims at the detection of primordial gravitational waves, which could have been produced during the inflationary period right after the birth of the Universe. There are many other scientific objectives of DECIGO, including the direct measurement of the acceleration of the expansion of the Universe, and reliable and accurate predictions of the timing and locations of neutron star/black hole binary coalescences. DECIGO consists of four clusters of observatories placed in heliocentric orbit. Each cluster consists of three spacecraft, which form three Fabry–Pérot Michelson interferometers with an arm length of 1000 km. Three DECIGO clusters will be placed far from each other, and the fourth will be placed in the same position as one of the other three to obtain correlation signals for the detection of primordial gravitational waves. We plan to launch B-DECIGO, which is a scientific pathfinder for DECIGO, before DECIGO in the 2030s to demonstrate the technologies required for DECIGO, as well as to obtain fruitful scientific results to further expand multi-messenger astronomy

Polypoidal choroidal vasculopathy

From the viewpoint of an Asian ophthalmologis

Movement of fluorescein and its glucuronide across retinal pigment epithelium-choroid. Invest Ophthalmol Vis Sci

Purpose. To characterize movement of fluorescein and its glucuronide across the blood-retinal barrier. Methods. Retinal pigment epithelium (RPE)-choroid preparations from New Zealand albino rabbit were sealed in an Ussing-type chamber in a stabilized condition for 3 hr, where movement of fluorescein and fluorescein glucuronide across the RPE-choroid was studied under a short circuit condition. Results. The outward (vitreous-choroid) permeability to fluorescein determined at a concentration of 15 fimo\/\ was about 4 times greater than the inward (choroid-vitreous) permeability (P &lt; 0.01). The outward permeability was significantly decreased by 50-65% by metabolic or competitive inhibitors (1 ^mol/1 ouabain, 10 ^inol/1 2,4-dinitrophenol, 100 ^mol/1 probenecid, 30 mmol/1 hippurate, or 5 mmol/1 iodipamide), whereas the inward permeability was not affected by any of the above competitive inhibitors. As the fluorescein concentration was increased from 15 to 150 /nmol/1, the net fluorescein movement across the tissue indicated saturation, and a Lineweaver-Burk plot gave an apparent K, n of 26 ^mol/1 and V max of 1.56 nmol/hr/cm 2 . The outward permeability to fluorescein glucuronide determined at 15 ^mol/1 was about double the inward permeability (P &lt; 0.01) and about !/s of the outward permeability to fluorescein (P &lt; 0.01). The outward permeability to fluorescein glucuronide was significantly decreased by about 50% by 1 /iinol/1 ouabain, 10 /umo/1 2,4-dinitrophenol, or 100 /iinol/l probenecid, whereas the inward permeability was not affected by 100 ^mol/1 probenecid. Conclusion. These results suggest that the majority of the outward fluorescein movement across the tissue and part of that of fluorescein glucuronide depends on an active transport mechanism, whereas the inward movement of both fluorescein and fluorescein glucuronide occurs by a passive mechanism. Invest Ophthalmol Vis Sci. 1993;34:531-538. JT luorescein has been widely used as a biologic marker to study the integrity of the blood-retinal barrier (BRB). Fluorescein fundus angiography has been the conventional method and is now complemented by the recently developed vitreous fluorophotometry. 1 In this method, the integrity of the BRB is calculated Medicine, Hongo, Tokyo, 113, Japan. based on the intensity of fluorescence in the vitreous cavity after systemic administration of fluorescein. When administered systemically, fluorescein is rapidly metabolized; its principal metabolite, fluorescein glucuronide, also is fluorescent, although weaker than that of fluorescein itself. &quot; 12 In the plasma, this metabolite reaches a much higher concentration than that of fluorescein and penetrates into the anterior chamber and the vitreous, where it represents a significant fraction of the total fluorescence. 10 &quot; 13 &quot; 15 In body fluids, fluorescein, an organic anion, is thought to act as a substrate for an active transport system in ocular tissues. 1617 In vivo studies have indi