VDAC in Retinal Health and Disease.

The retina, a tissue of the central nervous system, is vital for vision as its photoreceptors capture light and transform it into electrical signals, which are further processed before they are sent to the brain to be interpreted as images. The retina is unique in that it is continuously exposed to light and has the highest metabolic rate and demand for energy amongst all the tissues in the body. Consequently, the retina is very susceptible to oxidative stress.

Detection and verification of neurodegeneration after traumatic brain injury in the mouse: Immunohistochemical staining for amyloid precursor protein.

Previous studies of human traumatic brain injury (TBI) have shown diffuse axonal injury as varicosities or spheroids in white matter (WM) bundles when using immunoperoxidase-ABC staining with 22C11, a mouse monoclonal antibody against amyloid precursor protein (APP). These findings have been interpreted as TBI-induced axonal pathology. In a mouse model of TBI however, when we used immunofluorescent staining with 22C11, as opposed to immunoperoxidase staining, we did not observe varicosities or spheroids.

Concussion increases CA1 activity during prolonged inactivity in a familiar environment.

Although hippocampal damage plays a key role in impairments after concussion, differences in hippocampal information processing during recovery are unknown. Micro-endoscopic calcium imaging was performed before and after primary blast injury in freely behaving mice in two environments: their familiar home cage and a novel open field. Results show that after concussion CA1 activity increased in the familiar environment in which animals were awake and mostly immobile but was unaltered in a novel environment which the animals actively and constantly explored.

Primary blast injury causes cognitive impairments and hippocampal circuit alterations.

Blast-induced traumatic brain injury (bTBI) and its long term consequences are a major health concern among veterans. Despite recent work enhancing our knowledge about bTBI, very little is known about the contribution of the blast wave alone to the observed sequelae. Herein, we isolated its contribution in a mouse model by constraining the animals' heads during exposure to a shockwave (primary blast).

Lack of mGluR6-related cascade elements leads to retrograde trans-synaptic effects on rod photoreceptor synapses via matrix-associated proteins.

Heterotrimeric G-proteins couple metabotropic receptors to downstream effectors. In retinal ON bipolar cells, Go couples the metabotropic receptor mGluR6 to the TRPM1 channel and closes it in the dark, thus hyperpolarizing the cell. Light, via GTPase-activating proteins, deactivates Go , opens TRPM1 and depolarizes the cell.

Differential function of Gγ13 in rod bipolar and ON cone bipolar cells.

Heterotrimeric G-proteins (comprising Gα and Gβγ subunits) are critical for coupling of metabotropic receptors to their downstream effectors. In the retina, glutamate released from photoreceptors in the dark activates metabotropic glutamate receptor 6 (mGluR6) receptors in ON bipolar cells; this leads to activation of Go , closure of transient receptor potential melastatin 1 channels and hyperpolarization of these cells. Go comprises Gαo , Gβ3 and a Gγ.

PDE9A is expressed in the inner retina and contributes to the normal shape of the photopic ERG waveform.

The ubiquitous second messenger cGMP is synthesized by guanylyl cyclase and hydrolyzed by phosphodiesterase (PDE). cGMP mediates numerous signaling pathways in multiple tissues. In the retina, cGMP regulates signaling in nearly every cell class including photoreceptors, bipolar cells, amacrine cells, and ganglion cells.

Localization of Cacna1s to ON bipolar dendritic tips requires mGluR6-related cascade elements.

Purpose: L-type voltage gated calcium channels in retina localize primarily at the presynaptic active zones of photoreceptors and bipolar cells where they modulate glutamate release. However, the pore forming subunit Cacna1s of certain L-type channels is also expressed postsynaptically at the tips of ON bipolar cell dendrites where it colocalizes with mGluR6, but has an unknown function. At these dendritic tips, the components of the mGluR6 signaling cascade cluster together in a macromolecular complex, and each one's localization often depends on that of the others.

Kir2.4 surface expression and basal current are affected by heterotrimeric G-proteins.

Kir2.4, a strongly rectifying potassium channel that is localized to neurons and is especially abundant in retina, was fished with yeast two-hybrid screen using a constitutively active Gαo1. Here, we wished to determine whether and how Gαo affects this channel.

Effects of inhibition of neuronal nitric oxide synthase on basal retinal blood flow regulation.

Nitric oxide (NO) has been observed to regulate blood flow under basal and stimulated conditions in the retina. Recent evidence suggests that NO produced by neuronal nitric oxide synthase (nNOS) may regulate blood flow in addition to that produced by endothelial nitric oxide synthase (eNOS). The objective of the current study was to investigate the contribution of NO produced by nNOS in the regulation of basal retinal blood flow.

Scanning laser ophthalmoscope-particle tracking method to assess blood velocity during hypoxia and hyperoxia.

The main objective was to evaluate a Scanning Laser Ophthalmoscope (SLO) based particle tracking method as a means of quantitative assessment of retinal blood velocity and vessel diameter changes in response to hypoxia and hyperoxia. Retinal blood velocities were measured by tracking fluorescent microspheres (1.0 microm diameter) in anesthetized adult pigmented rats.

Computational modeling of factor Xa inhibition by immobilized tissue factor pathway inhibitor.

Coating surfaces of implanted devices with anticoagulants can reduce thrombosis and studies using a recombinant form of endogenous tissue factor pathway inhibitor (rTFPI) are promising. The anticoagulant function of immobilized rTFPI is thought to occur primarily by its inhibition of plasma clotting factor Xa (FXa); however the kinetics of this reaction at a surface are as yet unknown. To better understand the surface inhibition reaction under flow conditions, a theoretical model was developed delineating the roles of mass transport and reaction kinetics for an in vitro parallel plate device used in prior experimental studies [Hall et al.