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Intraretinal hyperreflective foci (HRF) are significant biomarkers for diabetic macular edema. However, HRF at the vitreoretinal interface (VRI) have not been examined in diabetic retinopathy (DR). A prospective observational clinical study with 162 consecutive eyes using OCT imaging showed significantly increased HRF at the VRI during DR progression (Pvegfa+/+) or Akimba (Akita × Kimba) mice (both PIns2+/-) mice, indicating macrophage activation was modulated by elevated VEGF rather than the diabetic milieu. Macrophage depletion significantly reduced HRF at the VRI (PCcr2rfp/+Cx3cr1gfp/+ vegfa+/- mice identified a significant contribution of M2-like tissue-resident macrophages (TRMs) at the VRI. Ki-67- and CD11b-positive cells were observed in preretinal tissues of DR patients while exposure of vitreal macrophages to vitreous derived from PDR patients induced a significant proliferation response in vitro (P

Detecting subtle vitreoretinal interface (VRI) findings, such as a posterior hyaloid membrane, is difficult with conventional retinal imaging. We compared ultra-high-resolution spectral domain optical coherence tomography (UHR-SD-OCT) with standard-resolution OCT (SD-OCT) for the imaging of VRI abnormalities in diabetic retinopathy (DR).This prospective cross-sectional study included 113 consecutive patients (91 patients with diabetes and 22 healthy controls). The VRI was evaluated, and the results were compared between the conventional SD-OCT and UHR-SD-OCT images. VRI findings were also investigated before and after internal limiting membrane peeling during vitrectomy for proliferative DR.A total of 159 eyes (87.4%) of 91 patients with diabetes were analyzed. UHR-SD-OCT could detect a hyperreflective layer at the VRI, in which en face OCT showed a membrane-like structure, termed the hyperreflective membrane (HRMe). The preoperative HRMe could not be detected in all patients with proliferative DR who underwent internal limiting membrane peeling during vitrectomy. Although the HRMe did not correlate with the DR stage, eyes with diabetic macular edema (DME) (64.5%) showed a significant HRMe with UHR-SD-OCT more frequently than those without DME (35.8%) (P = 0.005).UHR-SD-OCT can detect the HRMe at the VRI in DR eyes, particularly in eyes with DME. The HRMe may present a thickened posterior hyaloid membrane that contributes to DME development.UHR-SD-OCT detects slight changes in the VRI in DR eyes. In the future, it may help to elucidate the mechanism of DME formation.

Macrophages are the main infiltrating immune cells in choroidal neovascularization (CNV), a hallmark of the human wet, or neovascular age-related macular degeneration (AMD). Due to their plasticity and ability to adapt to the local microenvironment in a tissue-dependent manner, macrophages display polar functional phenotypes characterized by their cell surface markers and their cytokine profiles. We found accumulation of hemoglobin-scavenging cluster of differentiation 163 (CD163)(+) macrophages in laser-induced CNV lesions and higher expression of CD163(+) monocytes in the peripheral blood on day 7 post injury in mice. In comparison, CD80(+) macrophages did not differ with laser-injury in young or aged mice and did not significantly change in the peripheral blood of CNV mice. We examined the percentages of CD163(+), CD206(+), and CD80(+) monocytes in the peripheral blood of patients with wet AMD, patients with dry AMD, and in age-matched individuals without AMD as controls. Percentages of peripheral blood CD163(+) monocytes in both dry AMD (P < .001) and wet AMD (P < .05) were higher than in age-matched non-AMD controls, while there was no difference between the groups in the percentages of peripheral CD206(+) and CD80(+) monocytes. Further, serum level of soluble CD163 (sCD163) was elevated only in patients with wet AMD (P < .05). An examination of 40 cytokine levels across the study groups revealed that anti-VEGF treated patients with wet AMD, who showed no exudative signs on the day of blood drawing had a cytokine profile that was similar to that of non-AMD individuals. These results indicate that CD163 could be further evaluated for its potential as a useful marker of disease activity in patients with neovascular AMD. Future studies will address the origin and potential mechanistic role of CD163(+) macrophages in wet AMD pathologies of angiogenesis and leakage of blood components.

To investigate the relevance of microaneurysm morphology in optical coherence tomography angiography (OCTA) image averaging and fluorescein leakage in diabetic retinopathy (DR).In 38 consecutive patients with DR, ten consecutive 3- × 3-mm fovea-centered OCTA (HS100, Canon Inc., Tokyo, Japan) and fluorescein angiography (FA) were performed, and averaged OCTA images were created based on the 10 images. After detecting all microaneurysms in FA images, the morphology was classified into four types (focal bulge, saccular/pedunculated, fusiform, and mixed) using averaged OCTA images. The correlation between microaneurysm leakage in FA, retinopathy stage, and microaneurysm morphology was estimated.Thirty-eight eyes (50.0%) of the 33 patients were available for analysis, and 370 (63.5%) of the 583 FA-detected microaneurysms were morphologically classifiable (focal bulge, 46; saccular/pedunculated, 143; fusiform, 29; and mixed, 152) in OCTA. There was a significant correlation between stage and percentage of microaneurysm morphology and between morphology and the presence of leakage (P 0.0001 and P 0.01, respectively). The proportion of focal bulges decreased with stage progression, while the other three types increased with stage progression. The percentage of FA leakage for focal bulge, saccular/pedunculated, fusiform, and mixed was 41.3%, 66.4%, 82.8%, and 66.4%, respectively, and the fusiform type showed significant FA leakage.Microaneurysm morphology is correlated with the DR stage and FA leakage. Microaneurysm morphology recognition using OCTA image averaging may be useful for the clinical evaluation of DR.

Purpose No lymphatic vessels have been identified in the retina. This study investigated whether pathological VEGF-A–overexpressing diabetic retina causes lymphangiogenesis. Methods Three genetic mouse models of diabetic retinopathy (DR) (Akita [Ins2+/−], Kimba [vegfa+/+], and Akimba [Akita × Kimba] mice) were used. Retinas were examined by fundus photography, fluorescence angiography (FA), and immunostaining to detect lymphangiogenesis or angiogenesis. Lyve1-GFP (Lyve1EGFP/Cre) mice were used to examine Lyve1-expressing cells by immunostaining. Lymphatic-related factors were investigated in mouse retina and vitreous fluid from proliferative diabetic retinopathy (PDR) patients by RT-PCR and ELISA, respectively. Aged Kimba and Akimba mice were used to examine the retinal phenotype at the late phase of VEGF overexpression. Results FA and immunostaining showed retinal neovascularization in Kimba and Akimba mice but not wild-type and Akita mice. Immunohistochemistry showed that lymphangiogenesis was not present in the retinas of Akita, Kimba, or Akimba mice despite the significant upregulation of lymphatic-related factors (Lyve1, podoplanin, VEGF-A, VEGF-C, VEGF-D, VEGFR2, and VEGFR3) in the retinas of Kimba and Akimba mice by RT-PCR (P < 0.005). Furthermore, lymphangiogenesis was not present in aged Kimba or Akimba mice. Significantly increased numbers of Lyve1-positive cells present in the retinas of Kimba and Akimba mice, especially in the peripheral areas, were CD11b positive, indicating a macrophage population (P < 0.005). VEGF-C in PDR vitreous with vitreous hemorrhage (VH) was higher than in PDR without VH or a macular hole. Conclusions Retinal VEGF-A overexpression did not cause typical lymphangiogenesis despite upregulated lymphatic-related factors and significant Lyve1-positive macrophage infiltration.

Choroidal neovascularization (CNV) is a serious complication of age‑related macular degeneration. The aim of the present study was to investigate the expression and distribution of M1 and M2 macrophages in a laser‑induced CNV adult mouse model. The mRNA expression levels of M1, M2 and pan macrophage markers, and macrophage‑associated angiogenic cytokines, were determined by reverse transcription‑quantitative polymerase chain reaction. Immunofluorescence studies were performed to determine the location of the macrophages. The expression levels of M1 macrophage markers increased to a greater extent compared with M2 markers in the retinal pigment epithelium (RPE)‑choroid complexes following laser photocoagulation. By contrast, the expression levels of M2 macrophage markers increased primarily in the retinas. Immunofluorescence studies revealed that the increased number of cluster of differentiation (CD)206‑positive cells were located primarily in the retina, whereas the CD80‑positive cells were located around the site of CNVs in the RPE‑choroid. In addition, the M1‑associated cytokines increased to a greater extent in the RPE‑choroid complexes, whereas the M2‑associated cytokines were highly expressed in the retinas. These findings indicate that M1 and M2 macrophage numbers increased following CNV; however, the locations were different in this mouse model of laser‑induced CNV. The results of the present study suggest that M1 macrophages have a more direct role in inhibiting the development of CNV.

Approximately 40% of patients with diabetic macular edema (DME) are resistant to anti–vascular endothelial growth factor (VEGF) therapy (rDME). Here, we demonstrate that significant correlations between inflammatory cytokines and VEGF, as observed in naive DME, are lost in patients with rDME. VEGF overexpression in the mouse retina caused delayed inflammatory cytokine upregulation, monocyte/macrophage infiltration (CD11b+ Ly6C+ CCR2+ cells), macrophage/microglia activation (CD11b+ CD80+ cells), and blood-retinal barrier disruption due to claudin-5 redistribution, which did not recover with VEGF blockade alone. Phosphorylated protein analysis of VEGF-overexpressed retinas revealed rho-associated coiled-coil–containing protein kinase (ROCK) activation. Administration of ripasudil, a selective ROCK inhibitor, attenuated retinal inflammation and claudin-5 redistribution. Ripasudil also contributed to the stability of claudin-5 expression by both transcriptional enhancement and degradation suppression in inflammatory cytokine–stimulated endothelium. Notably, the anti-VEGF agent and the ROCK inhibitor were synergic in suppressing cytokine upregulation, monocyte/macrophage infiltration, macrophage/microglia activation, and claudin-5 redistribution. Furthermore, in vitro analysis confirmed that claudin-5 redistribution depends on ROCK2 but not on ROCK1. This synergistic effect was also confirmed in human rDME cases. Our results suggest that ROCK-mediated claudin-5 redistribution by inflammation is a key mechanism in the anti-VEGF resistance of DME.

In diabetic retinopathy (DR), OCT angiography (OCTA) could not image all fluorescein angiography (FA)-detected microaneurysms. We investigated whether multiple image averaging could enhance the microaneurysm detection capability of OCTA in patients with DR.Prospective and cross-sectional observational study.Consecutive 31 patients (n = 62 eyes) with DR.All eyes underwent FA and 3 × 3 mm fovea-centered OCTA images were obtained using 2 devices: RTVue XR Avanti (Optovue Inc, Fremont, CA) and OCT HS-100 (Canon Inc, Toyko, Japan). OCTA imaging (HS-100) was performed 10 consecutive times. Microaneurysm detection capability was compared among 5 OCTA images (single image, ×3, ×5, and ×10 averaged images and single scan image with the RTVue XR Avanti device).Microaneurysm detection capability and the correlation between microaneurysm clinical characteristics or morphology and the extent of image averaging required for OCTA detection.A total of 415 microaneurysms could be analyzed in 31 eyes from 25 patients. Microaneurysms detected on single image, ×3, ×5, and ×10 averaged OCTA images were 144 (34.7%), 227 (54.7%), 285 (68.7%), and 306 (73.7%), respectively. Microaneurysm detection capability was significantly increased with increased image averaging. Microaneurysm detection with OCTA was not correlated with retinal thickness, FA leakiness, and indocyanine green angiogram detection or the number of averaged images, whereas there was significant correlation between microaneurysm morphology and microaneurysm visibility by the image-averaging process for 4 morphologies, particular the focal bulge types (P0.01).In DR, multiple image averaging is useful for increasing the microaneurysm detection capability of OCTA, especially for focal bulge-type microaneurysms.

Objetivo: Comparar la efectividad de ranibizumab intravítreo (RIV) para el tratamiento del edema macular diabético (EMD) en ojos con y sin vitrectomía previa. Procedimientos: Evaluamos de manera prospectiva la mejor agudeza visual corregida (MAVC) y el grosor macular central (GMC) tras el tratamiento con RIV durante 6 meses. Resultados: No se observaron diferencias significativas en la MAVC o GMC inicial en ninguno de los dos grupos. En el grupo no vitrectomizado (n = 15), los cambios medios en la MAVC y GMC hasta el sexto mes de tratamiento con respecto al valor inicial resultaron significativos (p < 0,01). En el grupo vitrectomizado (n = 10), se observó una mejora más lenta, y la mejora media en la MAVC no resultó significativa (p = 0,5), aunque la media en la disminución del GMC sí que lo fue (p < 0,05). No se observaron diferencias significativas en los cambios medios en la MAVC y el GMC entre ambos grupos a los 6 meses del tratamiento. Conclusiones: La diferencia en la efectividad de RIV entre ambos grupos no resultó significativa. Ranibizumab intravítreo puede ser una opción de tratamiento incluso en pacientes vitrectomizados con EMD.

Fluorescein angiography (FA) has been conventionally used for detection of retinal nonperfused area (NPA) in diabetic retinopathy (DR) in spite of its qualitative evaluation. Optical coherence tomography angiography (OCTA) has been recently reported to be useful for the quantification of retinal vascular disorder in DR. In this study, we examined whether retinal flow density (FD) measurement in OCTA was useful for NPA detection in DR. The study included 41 eyes from 29 patients with DR who underwent FA and OCTA. Regions surrounded by arteries or veins were extracted in the OCTA image, and the FDs in each region were measured by Image J. Furthermore, each region was classified as NPA or perfused area (PA) in FA. The receiver operating characteristic (ROC) curve was prepared by logistic regression analysis of the FD. The AUC (area under the ROC curve) and cutoff value of FD were also calculated. Two hundred fifty-two regions were analyzed and classified into 38 NPA regions and 214 PA regions using FA. FD of each capillary plexus in NPA was significantly smaller than in PA (p

Purpose Our purpose is to evaluate the spatial bias of macular capillary dropout accompanying diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). Methods This study included 47 patients with diabetes and 29 healthy individuals who underwent OCTA. Retinal capillary flow density (FD) of 2.6 × 2.6 or 5.2 × 5.2 mm foveal area as well as the four divided areas (superior, inferior, temporal, nasal) without a foveal avascular zone (FAZ) at the superficial capillary plexus and deep capillary plexus (DCP) were measured respectively using ImageJ and NI Vision. Spatial biases of FD (orientation bias ratio and hierarchical bias ratio) and the correlation between FAZ and FD were examined. Results OCTA showed focal capillary dropout in DR patients. The orientation bias of FD was significantly higher in NPDR compared to NDR in the DCP (P = 0.03). The hierarchical bias of FD was significantly shifted to a DCP dominance with progression of DR (P < 0.01). In addition, the FD and FAZ area were significantly inversely correlated in both plexus in DR patients but not in healthy subjects (P < 0.01). Conclusions Area-divided OCTA quantification shows the appearance of spatial biases of macular capillary dropout with the onset of DR, suggesting that DR-related macular capillary dropout occurs locally and randomly. Future studies are necessary to determine the clinical relevance of the spatial pattern of capillary dropout in DR.

Rho-associated kinase (Rho-kinase/ROCK) was originally identified as an effector protein of the G protein Rho. Its involvement in various diseases, particularly cancer and cardiovascular disease, has been elucidated, and ROCK inhibitors have already been applied clinically for cerebral vasospasm and glaucoma. Vitreoretinal diseases including diabetic retinopathy, age-related macular degeneration, and proliferative vitreoretinoapthy are still a major cause of blindness. While anti-VEGF therapy has recently been widely used for vitreoretinal disorders due to its efficacy, attention has been drawn to new unmet needs. The importance of ROCK in pathological vitreoretinal conditions has also been elucidated and is attracting attention as a potential therapeutic target. ROCK is involved in angiogenesis and hyperpermeability and also in the pathogenesis of various pathologies such as inflammation and fibrosis. It has been expected that ROCK inhibitors will become new molecular target drugs for vitreoretinal diseases. This review summarizes the recent progress on the mechanisms of action of ROCK and their applications in disease treatment.

Histological studies from autopsy specimens have characterized hard exudates as a composition of lipid-laden macrophages or noncellular materials including lipid and proteinaceous substances (hyaline substances). However, the characteristics of hard exudates in living patients have not been examined due to insufficient resolution of existing equipment. In this study, we used adaptive optics scanning laser ophthalmoscopy (AO-SLO) to examine the characteristics of hard exudates in patients with retinal vascular diseases. High resolution imaging using AO-SLO enables morphological classification of retinal hard exudates into two types, which could not be distinguished either on fundus examination or by spectral domain optical coherence tomography (SD-OCT). One, termed a round type, consisted of an accumulation of spherical particles (average diameter of particles: 26.9 ± 4.4 μm). The other, termed an irregular type, comprised an irregularly shaped hyper-reflective deposition. The retinal thickness in regions with round hard exudates was significantly greater than the thickness in regions with irregular hard exudates (P = 0.02). This differentiation of retinal hard exudates in patients by AO-SLO may help in understanding the pathogenesis and clinical prognosis of retinal vascular diseases

Histological studies from autopsy specimens have characterized hard exudates as a composition of lipid-laden macrophages or noncellular materials including lipid and proteinaceous substances (hyaline substances). However, the characteristics of hard exudates in living patients have not been examined due to insufficient resolution of existing equipment. In this study, we used adaptive optics scanning laser ophthalmoscopy (AO-SLO) to examine the characteristics of hard exudates in patients with retinal vascular diseases. High resolution imaging using AO-SLO enables morphological classification of retinal hard exudates into two types, which could not be distinguished either on fundus examination or by spectral domain optical coherence tomography (SD-OCT). One, termed a round type, consisted of an accumulation of spherical particles (average diameter of particles: 26.9 ± 4.4 μm). The other, termed an irregular type, comprised an irregularly shaped hyper-reflective deposition. The retinal thickness in regions with round hard exudates was significantly greater than the thickness in regions with irregular hard exudates (P = 0.02). This differentiation of retinal hard exudates in patients by AO-SLO may help in understanding the pathogenesis and clinical prognosis of retinal vascular diseases.

Hypoxia-induced retinal neovascularization is a major pathological condition in many vision-threatening diseases. In the present study, we determined whether interleukin (IL)-12, a cytokine that regulates angiogenesis, plays a role in the neovascularization in a mouse model of oxygen-induced retinopathy (OIR). We found that the expressions of the mRNAs of both IL-12p35 and IL-12p40 were significantly reduced in the OIR retinas compared to that of the room air-raised control. The sizes of the avascular areas and neovascular tufts were larger in IL-12p40 knock-out (KO) mice than that in wild type (WT) mice. In addition, an intravitreal injection of recombinant IL-12 reduced both avascular areas and neovascular tufts. IL-12 injection enhanced the expressions of interferon-gamma (IFN-γ) and other downstream chemokines. In an in vitro system, IL-12 had no significant effect on tube formation of human retinal microvascular endothelial cells (HRECs). Moreover, a blockade of IFN-γ suppressed the inhibitory effect of IL-12 on pathological neovascularization. These results suggest that IL-12 plays important roles in inhibiting pathological retinal neovascularization.

Purpose: To compare the effectiveness of intravitreal ranibizumab (IVR) for diabetic macular edema (DME) between eyes with and without previous vitrectomy. Procedures: We prospectively assessed the best-corrected visual acuity (BCVA) and central macular thickness (CMT) after IVR for 6 months. Results: There were no significant differences in the baseline BCVA and CMT between both groups. In the nonvitrectomized group (n = 15), the mean changes of BCVA and CMT from baseline to month 6 were significant (p < 0.01). In the vitrectomized group (n = 10), the improvement appeared to be slower, and the mean BCVA improvement was not significant (p = 0.5), although the mean CMT decrease was significant (p < 0.05). There were no significant differences in the mean changes of BCVA and CMT between both groups at 6 months. Conclusions: The difference in the effectiveness of IVR between both groups was not significant. IVR can be a treatment option even for vitrectomized DME eyes.

Purpose Retinal vascular networks are observed as a layered structure residing in a nerve fiber layer and an inner nuclear layer of the retina. This study aimed to evaluate reflectance confocal adaptive optics scanning laser ophthalmoscopy (AO-SLO) for imaging of the layered retinal vascular networks. Methods This study included 16 eyes of 16 healthy cases. On the fovea, 2.8- and 3.0 mm2-areas were imaged using a prototype AO-SLO and optical coherence tomography angiography (OCTA), respectively. AO-SLO images focused on the nerve fiber and photoreceptor layers were recorded in the area. Two different vessel images (capillary networks in the superficial layer and in all layers) were generated to examine if the deep capillary network could be distinguished. We compared AO-SLO with OCTA in imaging of the layered retinal vascular networks. Results Sufficient images of capillary networks for analysis could be generated when the motion contrast was enhanced with AO-SLO movies in seven cases (43.8%). The deep capillary network could be distinguished in the merged image. Vascular depiction performance in AO-SLO was significantly better than in OCTA at both 0.5- and 1.0-mm areas from the fovea (P < 0.05). Conclusions Retinal vascular imaging using AO-SLO might be a useful adjunct to OCTA as a supportive method to evaluate the retina in healthy patients and patients with disease. Translational Relevance In cases requiring accurate and detailed retinal vasculature observation, AO-SLO might be useful for evaluating retinal vascular lesions as a supportive imaging method of OCTA.

To determine whether vitreal concentrations of MCP-1, IL-6 and IL-8 are altered after vitrectomy in patients with proliferative diabetic retinopathy (PDR) and to investigate whether the altered levels of these cytokines are associated with postoperative macular oedema.Vitreous samples were collected from 36 eyes of 33 patients with PDR before pars plana vitrectomy without intraocular lens (IOL) implantation, and also from the same 36 eyes during IOL implantation surgery approximately 7 months after the initial vitrectomy. Levels of MCP-1, IL-6, IL-8 and vascular endothelial growth factor were measured by flow cytometry using cytometric bead array (CBA) technology.The mean vitreous levels of MCP-1, IL-6 and IL-8 in the samples collected before vitrectomy were significantly higher in patients with PDR than in control patients (p0.0001). The levels of MCP-1 and IL-6 in the samples collected at the time of IOL implantation were significantly higher than those collected before vitrectomy (p0.05). In contrast, the level of IL-8 was significantly lower after vitrectomy (p0.05). The levels of IL-6 and IL-8, but not MCP-1, in the vitreous from eyes with PDR were inversely correlated with the interval between the initial vitrectomy and the time of implantation surgery. Among the vitrectomised patients, the mean vitreous level of MCP-1 in eyes with diabetic macular oedema (DME) was significantly higher than in those without DME (p=0.028).The elevated levels of MCP-1 and IL-6 may indicate prolonged inflammation even after successful vitrectomy, which can cause postoperative DME.

Purpose In this study, we investigated the therapeutic potential of a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor ripasudil (K-115) eye drop on retinal neovascularization and hypoxia. Methods In vitro, human retinal microvascular endothelial cells (HRMECs) were pretreated with ripasudil and then stimulated with VEGF. ROCK activity was evaluated by phosphorylation of myosin phosphatase target protein (MYPT)-1. Endothelial migration and cell viability were assessed by cell migration and MTT assay, respectively. The concentration of ripasudil in the retina was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In vivo, normal saline, 0.4%, or 0.8% ripasudil were administered three times a day to mice with oxygen-induced retinopathy (OIR). The areas of neovascularization and avascular retina were also quantified with retinal flat-mounts at postnatal day (P) 15, P17, or P21. The retinal hypoxic area was evaluated using hypoxia-sensitive drug pimonidazole by immunohistochemistry at P17. The vascular normalization was also evaluated by immunohistochemistry at P17. Results Ripasudil but not fasudil significantly reduced VEGF-induced MYPT-1 phosphorylation in HRMECs at 30 μmol/L. Ripasudil significantly inhibited VEGF-induced HRMECs migration and proliferation. The concentration of ripasudil in the retina was 3.8 to 10.4 μmol/L and 6.8 to 14.8 μmol/L after 0.4% and 0.8% ripasudil treatment, respectively. In the 0.4% and 0.8% ripasudil treated OIR mice, the areas of neovascularization as well as avascular area in the retina was significantly reduced compared with those of saline-treated mice at P17 and P21. Pimonidazole staining revealed that treatment with 0.4% and 0.8% ripasudil significantly inhibited the increase in the hypoxic area compared with saline. 0.8% ripasudil could cause intraretinal vascular sprouting and increase retinal vascular perfusion. Conclusions Novel ROCK inhibitor ripasudil eye drop has therapeutic potential in the treatment of retinal hypoxic neovascular diseases via antiangiogenic effects as well as vascular normalization.

Sudies were carried out to evaluate the surface active properties of rhamnolipid B [2-O- (2-O- α-decenoyl-α-L-rhamnopyranosyl) - α -L-rhamnopyranosyl-β-hydroxydecanoyl- β-hydroxydecanoic acid] and its precursor A as microbial biosurfactants produced by the hydro-carbon-assimilating bacterium, Pseudomonas aeruginosa BOP 100. The micelle formation of the sodium salts of rhamnolipids was confirmed by the detection of critical micelle concentration s (cmc) of A : 6.22 × 10-5, B : 1.50 × 10-4M (fluorescence intensity of ANS) and by micellar weight determinations of A : 38000, B : 7000 (light scattering), in spite of the bulky and complicated structures of the micelles, consisting of alternate hydrophobic and hydrophilic portions in contrast to synthetic surfactants. The γ cmc values of the sodium salts of A and B were 28 mN/m, while their interfacial tension was 0.2 and 3.2 mN/m at the interface between 0.1% solution and kerosene. Moreover, highly efficient gross effects were also noted particularly in dispersing, emulsifying, foaming and penetrating action. From these findings rhamnolipids may be concluded to have large surface activity and polyfunctionality on the basis of the amphiphiles as membranous constituents.

(1)福井県文室鉱山坑内水よりマンガン酸化能の優れたheterotrophicの一菌株(F 2)を分離した.同菌株は1,000mg/lの高濃度マンガン水溶液中に生育でき,水溶性マンガンを菌体表面で酸化し, MnO2を沈着した. (2)マンガン酸化活性の高い菌体生産のための最適培地は,ペプトン0.01%,クエン酸第二鉄アンモニウム0.01%およびMn2+ 100mg/lを含むものであった.温度は25°C,初発pHは7.0,撹絆は200 rpmが最適であった.これらの条件下における10日間の培養で,菌体収量は75.6mg/l,菌体1mg当りのMn4+沈着量は1.28mgであった. (3)マンガン沈着菌体を繰り返し使用する回分処理法により,有機栄養源を添加することなく,高濃度マンガン坑水の除マンガンを行うことができた.単位菌体当りのマンガン沈着量が多くなるほどマンガン酸化活性は高まった.菌体200mgを用いてMn2+ 450mg/lを含むマンガン坑水500mlを, 24時間以内でMn2+ 10mg/l以下に処理することができた. (4)本菌株の菌学的性質を検討した結果, Pseudomonas pseudoalcaligenesによく似た細菌であることを認めた.

Rhamnolipid B and its precursor A, both microbial and membranous constituent, reversibly changed morphologies of their molecular aggregates from vesicles under acidic conditions, to lamella, lipid particles, and finally to micelles under weakly acidic conditions within a narrow pH range of about 5–7.

In 1961, the Japan Nuclear Ship Research Association made a contract with the Science and Technical Agency of Japanese Government, on the trial design of nuclear powered oceanographic and supply ship as one of the latter's projects for the peaceful use of nuclear power. The association organized a committee to supervise the designing in which the author presided as the chairman. An outline description is given of the design which was completed in July, 1962. The ship has 6,350 gross tonnage and is equipped with a water-cooled, water-moderated pressurized water reactor which has 35 Mw thermal output and produces 10,000 shp. The weight of the trial design was not placed in developing a new type of marine reactor nor in detailing about conventional part of a ship's design. The main object was to study the feasibility of a comparatively small nuclear powered vessel with a proved-type reactor with satisfactory safety and also to find out where would the problems, technological and legal lie if such a ship was constructed in a very near future. (auth)

Background The purpose of this study was to report a case of traumatic maculopathy with para-central visual field defects following an impact by airbag deployment using adaptive optics scanning laser ophthalmoscopy (AO-SLO). Case presentation A 51-year-old man was involved in a motor vehicular accident and his left eye was struck by the deployed airbag, resulting in a para-central scotoma. The patient underwent a full ophthalmologic examination, spectral-domain optical coherence tomography (SD-OCT), and imaging with prototype AO-SLO systems (Canon Inc.) at 14 and 22 months after the injury. Images focused on the photoreceptor layer were recorded in the foveal area, and a montage of AO-SLO images was created. On AO-SLO, focal dark areas could be observed in the left eye at 14 months after the injury. The analysis showed that the cone mosaic (cone density, 16503/mm2; ratio of hexagonal Voronoi domain, 36.3 %; average nearest-neighbor distance (NND)/expected NND, 0.606) was disordered compared with the normal area of the same eye (cone density, 24821/mm2; ratio of hexagonal Voronoi domain, 44.1 %; average NND/expected NND, 0.739). The cone defect area corresponded to the area of the scotoma. A second AO-SLO was performed on the patient at 22 months after the injury and although there were still areas with reduced cone reflectivity, partial improvement of cone mosaic was detected by AO-SLO at this time point. Conclusion Partial recovery of damaged cone photoreceptors following closed globe blunt ocular trauma can be documented using AO-SLO longitudinal tracking.