Effects of Astaxanthin, Lutein, and Zeaxanthin on Eye-Hand Coordination and Smooth-Pursuit Eye Movement after Visual Display Terminal Operation in Healthy Subjects: A Randomized, Double-Blind Placebo-Controlled Intergroup Trial.

(1) Background: The impairment of eye-hand coordination and smooth-pursuit eye movement caused by visual display terminal (VDT) operation is thought to impair daily living activities, for which no effective methods are currently known. On the other hand, various food ingredients, including astaxanthin, lutein, and zeaxanthin, are known to help improve the eye health of VDT operators. This study aimed to test the hypothesis that the combination of astaxanthin, lutein, and zeaxanthin can prevent the impairment of eye-hand coordination and smooth-pursuit eye movement caused by VDT operation.

Mathematical analysis of phototransduction reaction parameters in rods and cones.

Retinal photoreceptor cells, rods and cones, convert photons of light into chemical and electrical signals as the first step of the visual transduction cascade. Although the chemical processes in the phototransduction system are very similar to each other in these photoreceptors, the light sensitivity and time resolution of the photoresponse in rods are functionally different than those in the photoresponses of cones. To systematically investigate how photoresponses are divergently regulated in rods and cones, we have developed a detailed mathematical model on the basis of the Hamer model.

Ablation of Ctrp9, Ligand of AdipoR1, and Lower Number of Cone Photoreceptors in Mouse Retina.

Purpose: C1q/TNF-related protein (CTRP) 9 is one of the adiponectin paralogs, and a genetic ablation of its receptor, AdipoR1, is known to cause retinal degeneration. The purpose of this study was to determine the role played by CTRP9 in the retina.

Methods: The retinas of Ctrp9 gene knockout (KO) and wild type (WT) mice were examined by electroretinography (ERG), histology, RNA sequencing, and quantitative real-time PCR.

Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior.

The 15q13.3 microdeletion syndrome is a genetic disorder characterized by a wide spectrum of psychiatric disorders that is caused by the deletion of a region containing 7 genes on chromosome 15 (MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7). The contribution of each gene in this syndrome has been studied using mutant mouse models, but no single mouse model recapitulates the whole spectrum of human 15q13.

Gene delivery to cone photoreceptors by subretinal injection of rAAV2/6 in the mouse retina.

Adeno-associated virus (AAV) has been studied as a safe delivery tool for gene therapy of retinal blinding diseases such as Leber's congenital amaurosis (LCA). The tropism of recombinant AAV (rAAV) including its specificity and efficiency in targeting retinal cell types has been studied with native or engineered capsids, along with specific promoters. However, one of the rAAV serotypes, rAAV2/6, has not been well-studied based on a report of low infection efficiency in the retina.

Adeno Associated Virus (AAV) as a Tool for Clinical and Experimental Delivery of Target Genes into the Mammalian Retina.

With an increasing number of identified causative genes, the widespread use of gene therapy is quickly becoming feasible. Once a target gene is selected, it is important to have a cell delivery method that is both specific and efficient. Cell type specificity and high efficiency is particularly important for the treatment of retinal degeneration, since viruses are efficient gene delivery vehicles for the nervous system, but often bring with them non-specific infections.

Evaluation of critical flicker-fusion frequency measurement methods using a touchscreen-based visual temporal discrimination task in the behaving mouse.

The critical flicker-fusion frequency (CFF), defined as the frequency at which a flickering light is indistinguishable from a continuous light, is a useful measure of visual temporal resolution. The mouse CFF has been studied by electrophysiological approaches such as recordings of the electroretinogram (ERG) and the visually evoked potential (VEP), but it has not been measured behaviorally. Here we estimated the mouse CFF by using a touchscreen based operant system.

[A Potential Mechanism for Spontaneous Oscillation in the Abnormal Retina].

　Rhythmic neural activities are observed in many brain regions, and these are considered to play an important role in neural information processing. On the other hand, distinct rhythmic neural activities emerge under several pathological conditions, suggesting that rhythmic neural activity has a close relation to brain function and dysfunction. In many pathological cases, the intrinsic property of unusual rhythm generation in a neuron or a neuronal network is prevented under normal conditions, but released by the pathological condition.

[Electrophysiological Analysis of Retinal Oscillation in Normal and Degenerated Retina].

　The vertebrate retina is one of the most sophisticated parts of the nervous system. It comprises five classes of neurons and one glial type cell. During development, but prior to a vertebrate's eyes opening, retinal circuits are refined by endogenous neural activity.

Expression of Quaking RNA-Binding Protein in the Adult and Developing Mouse Retina.

Quaking (QKI), which belongs to the STAR family of KH domain-containing RNA-binding proteins, functions in pre-mRNA splicing, microRNA regulation, and formation of circular RNA. QKI plays critical roles in myelinogenesis in the central and peripheral nervous systems and has been implicated neuron-glia fate decision in the brain; however, neither the expression nor function of QKI in the neural retina is known. Here we report the expression of QKI RNA-binding protein in the developing and mature mouse retina.

Reproducing retinal rod bipolar cell light response by mathematical model including neurotransmitter receptors.

Detailed mathematical model of retinal cells is useful for the quantitative understanding of the subcellular processes of the visual system. Retinal bipolar cells receive information from photoreceptor cells, horizontal cells and amacrine cells, thus it can be considered as information integration system. Despite its importance, bipolar cell model including inputs and outputs has not been proposed.

Depolarizing bipolar cell dysfunction due to a Trpm1 point mutation.

Mutations in TRPM1 are found in humans with an autosomal recessive form of complete congenital stationary night blindness (cCSNB). The Trpm1(-/-) mouse has been an important animal model for this condition. Here we report a new mouse mutant, tvrm27, identified in a chemical mutagenesis screen.

mGluR6 deletion renders the TRPM1 channel in retina inactive.

In darkness, glutamate released from photoreceptors activates the metabotropic glutamate receptor 6 (mGluR6) on retinal ON bipolar cells. This activates the G protein G(o), which then closes transient receptor potential melastatin 1 (TRPM1) channels, leading to cells' hyperpolarization. It has been generally assumed that deleting mGluR6 would render the cascade inactive and the ON bipolar cells constitutively depolarized.

miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression.

MicroRNA-124a (miR-124a) is the most abundant microRNA expressed in the vertebrate CNS. Despite past investigations into the role of miR-124a, inconsistent results have left the in vivo function of miR-124a unclear. We examined the in vivo function of miR-124a by targeted disruption of Rncr3 (retinal non-coding RNA 3), the dominant source of miR-124a.

A role for nyctalopin, a small leucine-rich repeat protein, in localizing the TRP melastatin 1 channel to retinal depolarizing bipolar cell dendrites.

Expression of channels to specific neuronal sites can critically impact their function and regulation. Currently, the molecular mechanisms underlying this targeting and intracellular trafficking of transient receptor potential (TRP) channels remain poorly understood, and identifying proteins involved in these processes will provide insight into underlying mechanisms. Vision is dependent on the normal function of retinal depolarizing bipolar cells (DBCs), which couple a metabotropic glutamate receptor 6 to the TRP melastatin 1 (TRPM1) channel to transmit signals from photoreceptors.

TRPM1: a vertebrate TRP channel responsible for retinal ON bipolar function.

The transient receptor potential (TRP) channels affect essential functions widely in sensory systems of various species, both invertebrates and vertebrates. The channel protein encoded by the trp gene, the first identified TRP superfamily molecule, is known to mediate the Drosophila light response. A vertebrate TRP channel playing a crucial role in the visual system has not yet been discovered, although numerous studies have revealed primal functions of TRP superfamily molecules in various sensory systems other than vision.

TRPM1 mutations are associated with the complete form of congenital stationary night blindness.

Purpose: To identify human transient receptor potential cation channel, subfamily M, member 1 (TRPM1) gene mutations in patients with congenital stationary night blindness (CSNB).

Methods: We analyzed four different Japanese patients with complete CSNB in whom previous molecular examination revealed no mutation in either nyctalopin (NYX) or glutamate receptor, metabotropic 6 (GRM6). The ophthalmologic examination included best-corrected visual acuity, refraction, biomicroscopy, ophthalmoscopy, fundus photography, Goldmann kinetic perimetry, color vision tests, and electroretinography (ERG).

Panky, a novel photoreceptor-specific ankyrin repeat protein, is a transcriptional cofactor that suppresses CRX-regulated photoreceptor genes.

Neuronal gene transcription is regulated by both transcriptional activators and repressors. While the roles of transactivators in retinal photoreceptor development have been well characterized, the roles of repressors have been poorly understood. We isolated Panky/Ankrd33, a gene encoding an ankyrin repeat-containing protein.

TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade.

An essential step in intricate visual processing is the segregation of visual signals into ON and OFF pathways by retinal bipolar cells (BCs). Glutamate released from photoreceptors modulates the photoresponse of ON BCs via metabotropic glutamate receptor 6 (mGluR6) and G protein (Go) that regulates a cation channel. However, the cation channel has not yet been unequivocally identified.

Functional roles of Otx2 transcription factor in postnatal mouse retinal development.

We previously reported that Otx2 is essential for photoreceptor cell fate determination; however, the functional role of Otx2 in postnatal retinal development is still unclear although it has been reported to be expressed in retinal bipolar cells and photoreceptors at postnatal stages. In this study, we first examined the roles of Otx2 in the terminal differentiation of photoreceptors by analyzing Otx2; Crx double-knockout mice. In Otx2+/-; Crx-/- retinas, photoreceptor degeneration and downregulation of photoreceptor-specific genes were much more prominent than in Crx-/- retinas, suggesting that Otx2 has a role in the terminal differentiation of the photoreceptors.

Cloning and characterization of mr-s, a novel SAM domain protein, predominantly expressed in retinal photoreceptor cells.

Background: Sterile alpha motif (SAM) domains are approximately 70 residues long and have been reported as common protein-protein interaction modules. This domain is found in a large number of proteins, including Polycomb group (PcG) proteins and ETS family transcription factors. In this work, we report the cloning and functional characterization of a novel SAM domain-containing protein, which is predominantly expressed in retinal photoreceptors and the pineal gland and is designated mouse mr-s (major retinal SAM domain protein).

Function of atypical protein kinase C lambda in differentiating photoreceptors is required for proper lamination of mouse retina.

The photoreceptor is a highly polarized neuron and also has epithelial characteristics such as adherens junctions. To investigate the mechanisms of polarity formation of the photoreceptor cells, we conditionally knocked out atypical protein kinase Clambda (aPKClambda), which has been proposed to play a critical role in the establishment of epithelial and neuronal polarity, in differentiating photoreceptor cells using the Cre-loxP system. In aPKClambda conditional knock-out (CKO) mice, the photoreceptor cells displayed morphological defects and failed to form ribbon synapses.