Wider Retinal Artery Trajectories in Eyes with Macular Hole Than in Fellow Eyes of Patients with Unilateral Idiopathic Macular Hole

Purpose

To determine whether the width of the retinal artery (RA) trajectory was associated with the presence of a macular hole (MH).

Methods

A retrospective cross sectional case-control study was performed. The fundus photographs were rotated 90 degrees, and the coordinates of the best fit curve of the RA trajectory were determined automatically based on these plots using the ImageJ program. The converted coordinates were fit to a second degree polynomial (ax²/100 + bx + c) equation. The width and steepness of the RA trajectory, “a”, of the eyes with a MH eye were compared to that of the fellow eyes.

Results

One hundred and ten eyes of 55 consecutive patients (30 women) with a unilateral MH and healthy fellow eyes were analyzed. The mean age was 64.9 years (range 47-81 years). The constant ‘a’ was significantly smaller in eyes with a MH than that of the fellow eyes (0.379 ± 0.094 vs 0.416 ± 0.121, P = 0.001, paired t test), indicating that the RA trajectory was wider in the MH eyes than in the fellow eyes. There was a significant correlation between the axial length and ‘a’ of the RA trajectory in the MH eyes (R = 0.273, P = 0.044) and in the fellow eyes (R = 0.356, P = 0.008; Spearman’s rank correlation coefficient).

Conclusions

Because eyes with a MH have a significantly wider and flatter RA trajectory, there may be greater traction on the fovea which is located between the RA arches. The causative role of this finding is still unclear.     

Measurement of local strain on cell membrane at initiation point of calcium signaling response to applied mechanical stimulus in osteoblastic cells

In adaptive bone remodeling, it is believed that bone cells such as osteoblasts, osteocytes and osteoclasts can sense mechanical stimuli and modulate their remodeling activities. However, the mechanosensing mechanism by which these cells sense mechanical stimuli and transduce mechanical signals into intracellular biochemical signals is still not clearly understood. From the viewpoint of cell biomechanics, it is important to clarify the mechanical conditions under which the cellular mechanosensing mechanism is activated. The aims of this study were to evaluate a mechanical condition, that is, the local strain on the cell membrane, at the initiation point of the intracellular calcium signaling response to the applied mechanical stimulus in osteoblast-like MC3T3-E1 cells, and to investigate the effect of deformation velocity on the characteristics of the cellular response. To apply a local deformation to a single cell, a glass microneedle was directly indented to the cell and moved horizontally on the cell membrane. To observe the cellular response and the deformation of the cell membrane, intracellular calcium ions and the cell membrane were labeled using fluorescent dyes and simultaneously observed by confocal laser scanning microscopy. The strain distribution on the cell membrane attributable to the applied local deformation and the strain magnitude at the initiation point of the calcium signaling responses were analyzed using obtained fluorescence images. From two-dimensionally projected images, it was found that there is a local compressive strain at the initiation point of calcium signaling. Moreover, the cellular response revealed velocity dependence, that is, the cells seemed to respond with a higher sensitivity to a higher deformation velocity. From the viewpoint of cell biomechanics, these results provide us a fundamental understanding of the mechanosensing mechanism of osteoblast-like cells.     

Production of anti-amyloid β antibodies in mice fed rice expressing amyloid β

The main signs of Alzheimer's disease (AD) are cognitive impairment and senile plaques composed of amyloid beta (Aβ) observed in patients' brains. Therefore, therapy for AD focuses on the removal of Aβ. We developed an "edible vaccine" that employs intestinal immunity with little to no side effects. Rice was utilized as an edible vaccine. It expressed GFP-Aβ42. Aβ rice was administered orally to wild-type (WT) mice causing production of anti-Aβ antibodies. Since Aβ rice was mixed with the cholera toxin B subunit (CTB), antibody against the rice seed protein was also produced. Then, mice were caused to develop immune tolerance against the rice seed protein by oral administration of Aβ rice mixed with CTB. The results indicated that only anti-Aβ antibodies were produced.     

Development of a new class of benzoylpyrrole-based PPARα/γ activators

Starting with a subtle blood glucose-lowering effect of a TGF-β inhibitor, we designed and synthesized a series of benzoylpyrrole-based carboxylic acids as PPARs activators. Among these compounds, 10sNa exhibited favorable blood glucose-lowering effect without body weight gain. We assume that the beneficial effect of 10sNa is attributed to not only its compound PPARα agonistic activity but also its PPARγ partial agonistic activity.     

Transgenic rice expressing amyloid β-peptide for oral immunization

Various vaccine therapies for Alzheimer's disease (AD) have been investigated. Here we report transgenic rice expressing amyloid β-peptide (Aβ). The Aβ42 gene fused with a green fluorescent protein gene was introduced into rice using the Agrobacterium method. When transgenic brown rice expressing Aβ was orally administered to mice, serum anti-Aβ antibody titers were elevated. The same results were observed when mice were fed boiled, transgenic brown rice. The results indicate that an edible vaccine against AD using rice may be feasible. A vaccine derived from rice would be far cheaper than existing medical vaccines.     

Seasonal population dynamics and production of Microsetella norvegica, a widely distributed but little-studied marine planktonic harpacticoid copepod

Microsetella norvegica is a widely distributed marine planktonicharpacticoid copepod, which is poorly known from the biologicalpoint of view. We investigated the seasonal population dynamicsandproduction of M. norvegica in the central part of the InlandSea of Japan. It occurred throughout the year, whilst its reproductionwas confined to the warm season between May and November. Theproportion of ovigerous females, which carry a single egg sac,was low (mean: 23.1%) in August and September, and high (53.6%)in October. Their brood size attained a maximum (mean: 15.8eggs per sac) in July and August and declined gradually to 6.2eggs in November. Duration time from egg laying to moultingto adulthood was temperature-dependent; it was 31.9 and 14.3days at 20 and 27°C, respectively, under excess food conditionsin the laboratory. An enormously high population abundance (7.32x 10⁴ individuals m^-3), which accounted for 86.5% of the totalcopepods, and biomass (69.6 mg C m^-3) gave an annual maximumproduction rate of 4.90 mg C m^-3 day^-1) in October. Naupliiand copepodites disappeared in December, and the overwinteringpopulation was represented by adults, mainly large females.Associations of M. norvegica with marine snow aggregates, whichhave often been found in oligotrophic waters, were not observedin the food-rich environment of the Inland Sea of Japan.     

Interactions among yeast protein-disulfide isomerase proteins and endoplasmic reticulum chaperone proteins influence their activities

We previously reported that the reductive activities of yeast protein-disulfide isomerase (PDI) family proteins did not completely explain their contribution to the viability of Saccharomyces cerevisiae (Kimura, T., Hosoda, Y., Kitamura, Y., Nakamura, H., Horibe, T., and Kikuchi, M. (2004) Biochem. Biophys. Res. Commun. 320, 359-365). In this study, we examined oxidative refolding activities and found that Mpd1p, Mpd2, and Eug1p exhibit activities of 13.8, 16.0, and 2.16%, respectively, compared with Pdi1p and that activity for Eps1p is undetectable. In analyses of interactions between yeast PDI proteins and endoplasmic reticulum molecular chaperones, we found that Mpd1p alone does not have chaperone activity but that it interacts with and inhibits the chaperone activity of Cne1p, a homologue of mammalian calnexin, and that Cne1p increases the reductive activity of Mpd1p. These results suggest that the interface between Mpd1p and Cne1p is near the peptide-binding site of Cne1p. In addition, Eps1p interacts with Pdi1p, Eug1p, Mpd1p, and Kar2p with dissociation constants (KD) in the range of 10(-7) to 10(-6). Interestingly, co-chaperone activities were completely suppressed in Eps1p-Pdi1p and Eps1p-Mpd1p complexes, although only Eps1p and Pdi1p have chaperone activity. The in vivo consequences of these results are discussed.     

Quantitative evaluation of threshold fiber strain that induces reorganization of cytoskeletal actin fiber structure in osteoblastic cells

The cytoskeletal stress fiber structure plays essential roles in various kinds of cellular functions such as shape maintenance, active motility and mechanosensing, and its structure is dynamically reorganized under each functional process. In known reorganization mechanisms of the stress fibers, a change in its mechanical condition has been suggested as one of the key mediators that affect the reorganization process. Some experimental studies have clarified that tension release in the stress fibers induces fiber depolymerization that is considered to be the initial phase of the reorganization process. However, quantitative mechanical values such as strain or stress that induce depolymerization have still not been evaluated. This study is aimed at the quantitative evaluation of the mechanical value that induces stress fiber depolymerization, to gain a basic understanding of the reorganization phenomenon from a mechanical viewpoint. Osteoblastic cells (MC3T3-E1) were cultured on prestretched silicone rubber substrate. Compressive deformation was applied to the cells by uniaxially releasing the prestretched substrate strain and change in the stress fiber structure was observed. The results indicated that the compressive strain magnitude, not in the whole cell body but in the stress fiber itself, is important to induce disassembly of the stress fiber structure. The existence of a threshold strain magnitude for initiating fiber disassembly was also suggested; the threshold strain magnitude was evaluated as approximately -0.20.     

Prevention of endotoxin-induced lethality in mice by calmodulin kinase activator

Porphyromonas gingivalis strain 381 lipid A showed lower activity in inducing interleukin (IL)-1alpha and IL-1beta production and cytokine mRNA expression than synthetic Escherichia coli lipid A (compound 506) in alveolar macrophages of C57BL/6 mice. Both the lipid As induced tumor necrosis factor alpha in alveolar macrophages and IL-6 in peritoneal macrophages. A calmodulin (CaM) antagonist, W-7, inhibited IL-1beta production and its mRNA expression induced by P. gingivalis lipid A but not compound 506 in alveolar macrophages. A CaM kinase activator reduced the induction of IL-1beta in the serum of mice when administered with compound 506, and protected the mice against the lethal toxicity. The modulation of a variety of intracellular enzymes including the CaM kinase may result in clinical control of endotoxic sepsis.