Clinical and Genetic Characteristics of Patients with Mild Hyperphenylalaninemia Identified by Newborn Screening Program in Japan.

Phenylketonuria (PKU) and hyperphenylalaninemia (HPA), both identified in newborn screening, are attributable to variants in . Reportedly, the p.R53H(c.

Effect of VCP modulators on gene expression profiles of retinal ganglion cells in an acute injury mouse model.

In glaucoma, retinal ganglion cells are damaged, leading to the progressive constriction of the visual field. We have previously shown that the valosin-containing protein (VCP) modulators, Kyoto University Substance (KUS)121 and KUS187, prevent the death of retinal ganglion cells in animal models of glaucoma, including the one generated by N-methyl-D-aspartate (NMDA)-induced neurotoxicity. KUSs appeared to avert endoplasmic reticulum (ER) stress by maintaining ATP levels, resulting in the protection of ganglion cells from cell death.

Roles of oncogenes and tumor-suppressor genes in osteoclastogenesis (Review).

Osteoporosis is a bone disease that poses a tremendous burden to health care. The receptor activator of nuclear factor-κB (RANK) and its ligand (RANKL) have been a major focus of this research field. RANKL signaling not only activates a variety of downstream signaling pathways required for osteoclast development, but crosstalk with other signaling pathways also adjusts bone homeostasis both in normal physiology and in bone disease.

PI3K/AKT signaling mediated by G protein‑coupled receptors is involved in neurodegenerative Parkinson's disease (Review).

Parkinson's disease (PD) is a common progressive and multifactorial neurodegenerative disease, characterized by the loss of midbrain dopaminergic neurons. Numerous pathological processes including, inflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalance, and apoptosis as well as genetic factors may lead to neuronal degeneration. Motor deficits in PD are due mostly to the progressive loss of nigrostriatal dopaminergic neurons.

PINK1 signaling in mitochondrial homeostasis and in aging (Review).

Mitochondrial dysfunction is involved in the pathology of Parkinson's disease, an age-associated neurodegenerative disorder. Phosphatase and tensin homolog (PTEN)-induced putative kinase protein 1 (PINK1) is responsible for the most common form of recessive Parkinson's disease. PINK1 is a mitochondrial kinase that is involved in mitrochondrial quality control and promotes cell survival.

Effective PI3K modulators for improved therapy against malignant tumors and for neuroprotection of brain damage after tumor therapy (Review).

Due to the key role in various cellular processes including cell proliferation and cell survival on many cell types, dysregulation of the PI3K/AKT pathway represents a crucial step of the pathogenesis in many diseases. Furthermore, the tumor suppressor PTEN negatively regulates the PI3K/AKT pathway through its lipid phosphatase activity, which is recognized as one of the most frequently deleted and/or mutated genes in human cancer. Given the pervasive involvement of this pathway, the development of the molecules that modulate this PI3K/AKT signaling has been initiated in studies which focus on the extensive effective drug discovery.

Neuroprotective effects of VCP modulators in mouse models of glaucoma.

Glaucoma is a major cause of adult blindness due to gradual death of retinal ganglion cells. Currently, no therapeutics are available for the protection of these cells from the cell death. We have recently succeeded in synthesizing novel compounds, KUSs (Kyoto University Substances), which can reduce cellular ATP consumption by specifically inhibiting the ATPase activities of VCP, a major ATPase in the cell, and we have shown that KUSs could mitigate the disease progression of rd10, a mouse model of retinitis pigmentosa, without any apparent side effects.

Roles of PTEN with DNA Repair in Parkinson's Disease.

Oxidative stress is considered to play key roles in aging and pathogenesis of many neurodegenerative diseases such as Parkinson's disease, which could bring DNA damage by cells. The DNA damage may lead to the cell apoptosis, which could contribute to the degeneration of neuronal tissues. Recent evidence suggests that PTEN (phosphatase and tensin homolog on chromosome 10) may be involved in the pathophysiology of the neurodegenerative disorders.

Changes in morphology and visual function over time in mouse models of retinal degeneration: an SD-OCT, histology, and electroretinography study.

Purpose: To examine the long-term natural course of retinal degeneration in rd10 and rd12 mice using serial spectral-domain optical coherence tomography (SD-OCT), electroretinography/electroretinograms (ERGs), and histological analysis.

Methods: Photoreceptor layer thickness and the ability to visualize photoreceptor ellipsoid zones were analyzed using SD-OCT images, and these images were compared with hematoxylin and eosin-stained sections and electron microscopy images. The a- and b-wave amplitudes of the ERGs were analyzed.

Asymmetry analysis of macular inner retinal layers for glaucoma diagnosis.

Purpose: To determine if asymmetry in thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer, ganglion cell complex, and total retina between upper and lower macula halves can predict glaucoma.

Design: Retrospective case-control series.

Methods: One hundred twenty-two eyes of 122 patients (30 normal eyes and 30 preperimetric, 31 early, and 31 advanced glaucoma eyes) were studied.

Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosa.

Neuroprotection may prevent or forestall the progression of incurable eye diseases, such as retinitis pigmentosa, one of the major causes of adult blindness. Decreased cellular ATP levels may contribute to the pathology of this eye disease and other neurodegenerative diseases. Here we describe small compounds (Kyoto University Substances, KUSs) that were developed to inhibit the ATPase activity of VCP (valosin-containing protein), the most abundant soluble ATPase in the cell.

Alterations in the neural and connective tissue components of glaucomatous cupping after glaucoma surgery using swept-source optical coherence tomography.

Purpose: To visualize changes in deep optic nerve head (ONH) structures following glaucoma surgery using (3-dimensional [3D]) swept-source optical coherence tomography (SS-OCT) and to determine the clinical and structural factors associated with postoperative lamina cribrosa (LC) and prelaminar neural tissue (PLT) changes.

Methods: In this prospective observational case series, SS-OCT thin-sliced datasets of the ONH covering a 3- × 3-mm area comprised of 256 B-scans (interval between scans = ∼12 μm) were obtained before and 3 months after the surgery and evaluated in 73 eyes of 73 patients with glaucoma. Bruch's membrane opening (BMO) and anterior LC boundary were manually delineated by two methods; one in every four B-scans (64 B-scans per eye) and 15 equally spaced horizontal B-scans in BMO area, excluding both ends (interval between scans = 96-120 μm).

Macular imaging in highly myopic eyes with and without glaucoma.

Purpose: To determine how evaluations of macular structures on spectral-domain optical coherence tomography compare with those of the optic disc and circumpapillary retinal nerve fiber layer (RNFL) in discriminating between highly myopic eyes with and without glaucoma.

Design: Retrospective, comparative study.

Methods: The appearances of ganglion cell layer and RNFL on Spectralis macular scans (Heidelberg Engineering) and optic disc on photographs were evaluated by 2 observers.

Imaging of localized retinal nerve fiber layer defects in preperimetric glaucoma using spectral-domain optical coherence tomography.

Purpose: To characterize preperimetric retinal nerve fiber layer (RNFL) defects on speckle noise-reduced spectral-domain optical coherence tomography (SD-OCT), and to determine whether detection of preperimetric RNFL defects can be improved by speckle noise reduction.

Patients And Methods: Thirty-two eyes of 32 patients with preperimetric glaucoma and 30 normal eyes of 30 volunteers underwent complete ophthalmic examinations and scanning by speckle noise-reduced SD-OCT (Spectralis), single-scan SD-OCT (RTVue-100), and single-scan time-domain (Stratus) OCT.

Results: All 40 RNFL defects identified by photography had angular widths <30 degrees and no disruption of RNFL reflectivity on Spectralis.

A novel method to detect local ganglion cell loss in early glaucoma using spectral-domain optical coherence tomography.

Purpose: To test the glaucoma-discriminating ability of a new method for detecting local ganglion cell loss using spectral-domain optical coherence tomography (OCT).

Methods: This study included 58 glaucomatous and 48 healthy eyes from Japanese subjects. Combined thickness of the ganglion cell layer and inner plexus layer (GCIPL) was measured on a macular cube scan in Cirrus HD-OCT.

Retinal nerve fiber layer defects in highly myopic eyes with early glaucoma.

Purpose: To compare the retinal nerve fiber layer (RNFL) defects in early glaucomatous eyes between highly and non-highly myopic eyes.

Methods: Sixty-one highly myopic eyes (< -6.0 diopters [D]) of 61 patients and 55 non-highly myopic eyes of 55 patients with early visual field (VF) defects were studied.

Wide 3-dimensional macular ganglion cell complex imaging with spectral-domain optical coherence tomography in glaucoma.

Purpose: To determine whether measurement of ganglion cell complex (GCC) thickness over a wide area (8-mm diameter) can improve the glaucoma-discriminating ability of spectral-domain optical coherence tomography (SD-OCT) compared to that in the standard macular area (6-mm diameter).

Methods: Ninety-three subjects were enrolled, including 46 healthy eyes of 46 volunteers and 47 eyes of 47 glaucoma patients (23 eyes with preperimetric glaucoma [PPG] and 24 eyes with early glaucoma [EG]). All patients underwent SD-OCT raster scanning over a 9 mm × 9 mm square area centered on the fovea.

Frequency-doubling technology and retinal measurements with spectral-domain optical coherence tomography in preperimetric glaucoma.

Background: To determine the relationship between visual fields and retinal structures measured with spectral-domain optical coherence tomography in preperimetric glaucoma (PPG).

Methods: Twenty-six eyes of 26 patients with PPG and 20 healthy eyes of 20 volunteers were included. All patients underwent Heidelberg retina tomography-2 (HRT2), standard automated perimetry (SAP), frequency-doubling technology (FDT) perimetry, and RTVue-100.

Real-time imaging of rabbit retina with retinal degeneration by using spectral-domain optical coherence tomography.

Background: Recently, a transgenic rabbit with rhodopsin Pro 347 Leu mutation was generated as a model of retinitis pigmentosa (RP), which is characterized by a gradual loss of vision due to photoreceptor degeneration. The purpose of the current study is to noninvasively visualize and assess time-dependent changes in the retinal structures of a rabbit model of retinal degeneration by using speckle noise-reduced spectral-domain optical coherence tomography (SD-OCT).

Methodology/principal Findings: Wild type (WT) and RP rabbits (aged 4-20 weeks) were investigated using SD-OCT.

Longitudinal and simultaneous imaging of retinal ganglion cells and inner retinal layers in a mouse model of glaucoma induced by N-methyl-D-aspartate.

Purpose: To investigate the longitudinal profile of N-methyl-D-aspartate (NMDA) injection-induced damage in retinal ganglion cells (RGCs) by imaging retinal Thy 1-cyan fluorescent protein (CFP) expression and inner retinal layers using a custom-made imaging device containing short-wavelength confocal scanning laser ophthalmoscope (scSLO) and speckle noise-reduced spectral-domain optical coherence tomography (SD-OCT).

Methods: Simultaneous scSLO and SD-OCT examinations were performed in Thy 1-CFP mice injected with NMDA (1-20 nanomoles). CFP-expressing RGCs were counted using scSLO images.

Macular ganglion cell layer imaging in preperimetric glaucoma with speckle noise-reduced spectral domain optical coherence tomography.

Objective: To visualize the macular ganglion cell layer (GCL) and measure its thickness in normal eyes and eyes with preperimetric glaucoma, using speckle noise-reduced spectral domain optical coherence tomography (SD-OCT).

Design: Retrospective consecutive case series.

Participants: Thirty-seven eyes of 37 patients with preperimetric glaucoma and 39 normal eyes of 39 volunteers.

Biometric features of peripapillary atrophy beta in eyes with high myopia.

Purpose: To evaluate peripapillary atrophy β (PPA-β) characteristics in highly myopic eyes, using simultaneous confocal scanning laser ophthalmoscopy (cSLO) and enhanced spectral-domain optical coherence tomography (SD-OCT).

Methods: The authors retrospectively analyzed 61 highly myopic (≥ -6.0 D) eyes without myopic retinopathy.

Detection of localized retinal nerve fiber layer defects in glaucoma using enhanced spectral-domain optical coherence tomography.

Objective: To compare retinal nerve fiber layer (RNFL) defects on fundus photographs with circumpapillary RNFL (cpRNFL) thinning or disruption on images obtained by speckle-noise-reduced spectral-domain optical coherence tomography (enhanced SD OCT), single-scan SD OCT, and single-scan time-domain OCT (TD OCT).

Design: Retrospective, comparative case series.

Participants: Forty-four eyes of 44 patients with open-angle glaucoma with localized, wedge-shaped RNFL defects on red-free photographs and 35 normal eyes of 35 volunteers.

Monitoring of the sleep patterns of shift workers in the automotive industry.

Objective: The effect of shift schedules on the amount of sleep that workers receive is an important factor in workplace health and safety as well as the employees' overall quality of life. The objective of this study is to compare sleep period among workers engaging in each of the three-shift work.

Methods And Participants: The amount of sleep (sleep period) that male workers with rotating shift schedules received was measured using accelerometers.

Early trabeculectomy bleb walls on anterior-segment optical coherence tomography.

Background: To correlate the cross-sectional features of filtering blebs on anterior-segment optical coherence tomography (AS-OCT) 2 weeks after trabeculectomy with bleb function at 6 months.

Methods: Forty-eight eyes followed for 6 months or more after trabeculectomy with mitomycin C were included. Bleb wall reflectivity of developing blebs on AS-OCT 2 weeks postoperatively was correlated with mature bleb function at 6-month postoperative visit.