The neuroprotective effect of latanoprost acts via klotho-mediated suppression of calpain activation after optic nerve transection.

Latanoprost was first developed for use in glaucoma therapy as an ocular hypotensive agent targeting the prostaglandin F2α (FP) receptor. Subsequently, latanoprost showed a neuroprotective effect, an additional pharmacological action. However, although it is well-known that latanoprost exerts an ocular hypotensive effect via the FP receptor, it is not known whether this is also true of its neuroprotective effect.

Correlation of papillomacular nerve fiber bundle thickness with central visual function in open-angle glaucoma.

Purpose. To determine the correlation of reduced retinal thickness in the central papillomacular bundle (CPB) to central visual function, including central retinal sensitivity and visual acuity, in glaucoma patients. Methods.

Fiber-based polarization-sensitive OCT for birefringence imaging of the anterior eye segment.

We demonstrate a prototype system of polarization-sensitive optical coherence tomography (PS-OCT) designed for clinical studies of the anterior eye segment imaging. The system can measure Jones matrices of the sample with depth-multiplexing of two orthogonal incident polarizations and polarization-sensitive detection. An optical clock is generated using a quadrature modulator and a logical circuit to double the clock frequency.

Correlation of optic nerve microcirculation with papillomacular bundle structure in treatment naive normal tension glaucoma.

Purpose. To assess the association between optic nerve head (ONH) microcirculation, central papillomacular bundle (CPB) structure, and visual function in eyes with treatment naive normal tension glaucoma (NTG). Methods.

Characteristics of uveitic glaucoma and evaluation of its surgical treatment.

Purpose: To investigate the characteristics of uveitic glaucoma (UG) and evaluate surgical treatments.

Methods: This study examined a retrospective, nonrandomized comparative interventional case series of 105 UG patients (141 eyes) followed between April 1, 2001 and July 30, 2014 at the outpatient clinic of Tohoku University Hospital. The study group included 47 patients (47 eyes) who underwent glaucoma surgery: trabeculectomy, trabeculotomy, and trabectome surgery.

Retinal transcriptome profiling at transcription start sites: a cap analysis of gene expression early after axonal injury.

Background: Glaucoma is characterized by progressive loss of the visual field and death of retinal ganglion cells (RGCs), a process that is mediated, in part, by axonal injury. However, the molecular pathomechanisms linking RGC death and axonal injury remain largely unknown. Here, we examined these mechanisms with a cap analysis of gene expression (CAGE), which allows the comprehensive quantification of transcription initiation across the entire genome.

The novel Rho kinase (ROCK) inhibitor K-115: a new candidate drug for neuroprotective treatment in glaucoma.

Purpose: To investigate the effect of K-115, a novel Rho kinase (ROCK) inhibitor, on retinal ganglion cell (RGC) survival in an optic nerve crush (NC) model. Additionally, to determine the details of the mechanism of K-115's neuroprotective effect in vivo and in vitro.

Methods: ROCK inhibitors, including K-115 and fasudil (1 mg/kg/d), or vehicle were administered orally to C57BL/6 mice.

The role of calpain in an in vivo model of oxidative stress-induced retinal ganglion cell damage.

Purpose: In this study, we set out to establish an in vivo animal model of oxidative stress in the retinal ganglion cells (RGCs) and determine whether there is a link between oxidative stress in the RGCs and the activation of calpain, a major part of the apoptotic pathway.

Materials And Methods: Oxidative stress was induced in the RGCs of C57BL/6 mice by the intravitreal administration of 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH, 30mM, 2μl). Control eyes were injected with 2μl of vehicle.

The traditional kampo medicine tokishakuyakusan increases ocular blood flow in healthy subjects.

The aim of this study was to examine the effects of oral administration of kampo medical formulas on ocular blood flow (OBF). A crossover protocol was used to randomly administer five grams of yokukansan, tokishakuyakusan (TSS), keishibukuryogan, or hachimijiogan to 13 healthy blinded subjects (mean age: 37.3 ± 12.

Critical neuroprotective roles of heme oxygenase-1 induction against axonal injury-induced retinal ganglion cell death.

Although axonal damage induces significant retinal ganglion cell (RGC) death, small numbers of RGCs are able to survive up to 7 days after optic nerve crush (NC) injury. To develop new treatments, we set out to identify patterns of change in the gene expression of axonal damage-resistant RGCs. To compensate for the low density of RGCs in the retina, we performed retrograde labeling of these cells with 4Di-10ASP in adult mice and 7 days after NC purified the RGCs with fluorescence-activated cell sorting.

RNA sequence reveals mouse retinal transcriptome changes early after axonal injury.

Glaucoma is an ocular disease characterized by progressive retinal ganglion cell (RGC) death caused by axonal injury. However, the underlying mechanisms involved in RGC death remain unclear. In this study, we investigated changes in the transcriptome profile following axonal injury in mice (C57BL/6) with RNA sequencing (RNA-seq) technology.

Waveform analysis of ocular blood flow and the early detection of normal tension glaucoma.

Purpose: To investigate waveform changes in blood flow (BF) in the optic nerve head (ONH) and to evaluate their usefulness in identifying normal tension glaucoma (NTG).

Methods: Sixty-one eyes of 61 patients with NTG and 21 eyes of age-matched healthy control subjects were included in this study. The NTG eyes were divided into the following three groups based on the progression of their visual field defects: mild (mean deviation [MD] greater than -6.

Simulated visual fields produced from macular RNFLT data in patients with glaucoma.

Purpose: We investigated in detail the correlation between structure and function in the macula, and whether optical coherence tomography (OCT)-measured macular structure could be used to simulate the visual field.

Materials And Methods: This study comprised 60 eyes of 34 patients with open angle glaucoma (Anderson-Patella classification). To assess macular function, reliable data from the Humphrey field analyzer (HFA, SITA-standard, 10-2 program) for threshold, total deviation (TD), and pattern deviation (PD) were used.

Development of a new strategy of visual field testing for macular dysfunction in patients with open angle glaucoma.

Purpose: To explore methods of automated visual field (VF) examination for the assessment of macular function.

Method: We used a VF examination (AP-7000 automatic perimeter, Kowa, Japan) to examine macular function in 53 eyes from 29 patients with open angle glaucoma. We measured the mean total deviation (c-MD) of 16 points in the central VF located in a 2-degree-interval 4 × 4 array with various stimulus sizes (Goldmann sizes III, II, and I).

Critical role of Nrf2 in oxidative stress-induced retinal ganglion cell death.

NF-E2 related factor 2 (Nrf2) is a key transcription factor that plays a pivotal role in endogenous protection against oxidative stress. However, the role of Nrf2 in visual disorders remains unclear. It has been reported that oxidative stress is thought of as one of the causes of glaucoma.

The influence of posture change on ocular blood flow in normal subjects, measured by laser speckle flowgraphy.

Purpose: To investigate, using laser speckle flowgraphy (LSFG), the autoregulation of ocular blood flow (BF) in response to posture change.

Methods: This study comprised 20 healthy volunteers (mean age 30.0 ± 8.

Metabolic stress response implicated in diabetic retinopathy: the role of calpain, and the therapeutic impact of calpain inhibitor.

To describe how a high fat diet (HFD) and hyperglycemia initiate a sequence of calpain activation and oxidative stress associated with neuro-degenerative changes in diabetic retinopathy (DR), hyperglycemia was induced with streptozotocin in mice lacking the gene for calpastatin (CAST KO), and in mice lacking the gene for the transcription factor NF-E2 related factor 2 (Nrf2 KO). All animals were fed a HFD. Retinal ganglion cell (RGC) density was estimated by labeling with fluorogold and immunohistochemistry.

Progression of visual field defects in eyes with different optic disc appearances in patients with normal tension glaucoma.

Purpose: To investigate the relationship between the optic disc appearance and the progression of visual field defects in eyes with normal tension glaucoma (NTG).

Methods: Two hundred nine patients with NTG, who were being treated with topical antiglaucoma drugs and had been followed for at least 3 years, were studied. The baseline optic disc appearance was classified into 4 types: focal ischemic (FI), myopic glaucomatous (MY), senile sclerotic (SS), and generalized cup enlargement (GE).

Critical role of calpain in axonal damage-induced retinal ganglion cell death.

Calpain, an intracellular cysteine protease, has been widely reported to be involved in neuronal cell death. The purpose of this study is to investigate the role of calpain activation in axonal damage-induced retinal ganglion cell (RGC) death. Twelve-week-old male calpstatin (an endogenous calpain inhibitor) knockout mice (CAST KO) and wild-type (WT) mice were used in this study.

Tumor necrosis factor-alpha mediates photoreceptor death in a rodent model of retinal detachment.

Purpose: Photoreceptor degeneration is a major cause of visual loss in various retinal diseases, including retinal detachment (RD) and neovascular AMD, but the underlying mechanisms remain elusive. In this study, the role of TNFα in RD-induced photoreceptor degeneration was investigated.

Methods: RD was induced by subretinal injection of hyaluronic acid.

Suppression of phagocytic cells in retinal disorders using amphiphilic poly(γ-glutamic acid) nanoparticles containing dexamethasone.

To investigate the potential of nanoparticles (NPs) composed of poly(γ-glutamic acid) conjugated with l-phenylalanine (γ-PGA-Phe NPs) for the treatment of retinal diseases, γ-PGA-Phe NPs (200nm) were tested with macrophages and microglia in vitro or by intravitreal administration into normal or pathological rat eyes. The anti-inflammatory effects of the NPs containing dexamethasone (DEX-NPs) were examined using qRT-PCR in vitro by counting activated microglia and Fluorogold-labeled retinal ganglion cells in the retinas under excitotoxicity or by counting TUNEL (+) photoreceptors in the detached retinas. The NPs were taken up efficiently by cultured macrophages or microglia.

Association between primary open-angle glaucoma and WDR36 DNA sequence variants in Japanese.

Purpose: To determine whether mutations in the WD repeat domain 36 gene (WDR36) are associated with primary open-angle glaucoma (POAG) in Japanese. Subjects with high tension glaucoma (HTG) and normal tension glaucoma (NTG) were analyzed separately.

Methods: One hundred and thirty-six unrelated Japanese patients with HTG and 103 unrelated patients with NTG were studied.

ERK1 plays a critical protective role against N-methyl-D-aspartate-induced retinal injury.

Excitotoxicity has been implicated in several ischemic diseases of the retina, including retinal vessel occlusion and diabetic retinopathy. Glutamate signaling mediated through the N-methyl-D-aspartate (NMDA) receptor contributes to ischemic cell death. The NMDA receptor antagonists MK-801 and memantine have substantial neuroprotective effects in experimental retinal disease models, but the mechanisms by which NMDA receptor activity leads to cell death is not clear.