scholarly journals Characterization of Scotopic and Mesopic Rod Signaling Pathways in Dogs Using the On-Off Electroretinogram

2021 ◽  
Author(s):  
Nate Pasmanter ◽  
Simon M Petersen-Jones
Keyword(s):  
Signaling Pathways ◽  
Bipolar Cells ◽  
Rod Photoreceptor ◽  
Stimulus Strength ◽  
Full Field ◽  
Cell Responses ◽  
Lighting Conditions ◽  
Rod And Cone Photoreceptors ◽  
Rod Bipolar Cells

Abstract Background: The On-Off, or long flash, full field electroretinogram (ERG) separates retinal responses to flash onset and offset. Depending on degree of dark-adaptation and stimulus strength the On and Off ERG can be shaped by rod and cone photoreceptors and postreceptoral cells, including ON and OFF bipolar cells. Interspecies differences have been shown, with predominantly positive Off-response in humans and other primates and a negative Off-response in rodents and dogs. However, the rod signaling pathways that contribute to these differential responses have not been characterized. In this study, we designed a long flash protocol in the dog that varied in background luminance and stimulus strength allowing for some rod components to be present to better characterize how rod pathways vary from scotopic to mesopic conditions.Results: With low background light the rod a-wave remains while the b-wave is significantly reduced resulting in a predominantly negative waveform in mesopic conditions. Through modeling and subtraction of the rod-driven response, we show that rod bipolar cells saturate with dimmer backgrounds than rod photoreceptors, resulting in rod hyperpolarization contributing to a large underlying negativity with mesopic backgrounds. Conclusions: Reduction in rod bipolar cell responses in mesopic conditions prior to suppression of rod photoreceptor responses may reflect the changes in signaling pathway of rod-driven responses needed to extend the range of lighting conditions over which the retina functions.

Inhibitory Feedback Shapes Bipolar Cell Responses in the Rabbit Retina

2007 ◽  
Vol 98 (6) ◽  
pp. 3423-3435 ◽  
Author(s):  
Alyosha Molnar ◽  
Frank Werblin
Keyword(s):  
Bipolar Cell ◽  
Light Response ◽  
Bipolar Cells ◽  
Inhibitory Input ◽  
Rabbit Retina ◽  
Cell Responses ◽  
Inhibitory Feedback ◽  
Glycinergic Inhibition ◽  
Rod Bipolar Cells ◽  
Cone Bipolar Cells

Retinal bipolar cells can be divided into on and off types based on the polarity of their response to light. Bipolar activity is further shaped by inhibitory inputs, characterized here by the events that occur immediately after the onset of a light step: 1) in most off bipolar cells, excitatory current decreased, whereas inhibitory current increased. These currents reinforced each other, enhancing the light response. 2) In about half of the on cone bipolar cells, the excitatory current increased, whereas inhibitory current decreased, also reinforcing the light response. Both of these reinforcing interactions were mediated by glycinergic inhibition. 3) In the remaining on cone bipolar cells, excitation and inhibition both increased, but inhibition was delayed so that these cells responded transiently. 4) Finally, in rod bipolar cells, excitation and inhibition both increased so that inhibition suppressed excitation, reducing the light response at all time scales. The suppressive inhibition seen in on cone and rod bipolar cells was mediated by GABA. Thus morphologically diverse bipolar cells receive only four main types of inhibitory input, and the majority of “inhibitory” inputs actually serve to enhance excitation.

scholarly journals Multiple pathways of inhibition shape bipolar cell responses in the retina

2010 ◽  
Vol 28 (1) ◽  
pp. 95-108 ◽  
Author(s):  
ERIKA D. EGGERS ◽  
PETER D. LUKASIEWICZ
Keyword(s):  
Signaling Pathways ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Receptor Expression ◽  
Inner Plexiform Layer ◽  
Cell Responses ◽  
Receptor Inhibition ◽  
Light Signals ◽  
Glycinergic Inhibition

AbstractBipolar cells (BCs) are critical relay neurons in the retina that are organized into parallel signaling pathways. The three main signaling pathways in the mammalian retina are the rod, ON cone, and OFF cone BCs. Rod BCs mediate incrementing dim light signals from rods, and ON cone and OFF cone BCs mediate incrementing and decrementing brighter light signals from cones, respectively. The outputs of BCs are shaped by inhibitory inputs from GABAergic and glycinergic amacrine cells in the inner plexiform layer, mediated by three distinct types of inhibitory receptors: GABAA, GABAC, and glycine receptors. The three main BC pathways receive distinct forms of inhibition from these three receptors that shape their light-evoked inhibitory signals. Rod BC inhibition is dominated by slow GABAC receptor inhibition, while OFF cone BCs are dominated by glycinergic inhibition. The inhibitory inputs to BCs are also shaped by serial inhibitory connections between GABAergic amacrine cells that limit the spatial profile of BC inhibition. We discuss our recent studies on how inhibitory inputs to BCs are shaped by receptor expression, receptor properties, and neurotransmitter release properties and how these affect the output of BCs.

scholarly journals Knock-Out of Tenascin-C Ameliorates Ischemia-Induced Rod-Photoreceptor Degeneration and Retinal Dysfunction

2021 ◽  
Vol 15 ◽  
Author(s):  
Susanne Wiemann ◽  
Aisha Yousf ◽  
Stephanie C. Joachim ◽  
Carolin Peters ◽  
Ana M. Mueller-Buehl ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Photoreceptor Cell ◽  
Retinal Ischemia ◽  
Bipolar Cells ◽  
Rod Photoreceptor ◽  
Photoreceptor Degeneration ◽  
Wild Type ◽  
Knock Out ◽  
Retinal Thinning ◽  
Rod Bipolar Cells

Retinal ischemia is a common pathomechanism in various eye diseases. Recently, evidence accumulated suggesting that the extracellular matrix (ECM) glycoprotein tenascin-C (Tnc) plays a key role in ischemic degeneration. However, the possible functional role of Tnc in retinal ischemia is not yet known. The aim of our study was to explore retinal function and rod-bipolar/photoreceptor cell degeneration in wild type (WT) and Tnc knock-out (KO) mice after ischemia/reperfusion (I/R) injury. Therefore, I/R was induced by increasing intraocular pressure in the right eye of wild type (WT I/R) and Tnc KO (KO I/R) mice. The left eye served as untreated control (WT CO and KO CO). Scotopic electroretinogram (ERG) recordings were performed to examine rod-bipolar and rod-photoreceptor cell function. Changes of Tnc, rod-bipolar cells, photoreceptors, retinal structure and apoptotic and synaptic alterations were analyzed by immunohistochemistry, Hematoxylin and Eosin staining, Western blot, and quantitative real time PCR. We found increased Tnc protein levels 3 days after ischemia, while Tnc immunoreactivity decreased after 7 days. Tnc mRNA expression was comparable in the ischemic retina. ERG measurements after 7 days showed lower a-/b-wave amplitudes in both ischemic groups. Nevertheless, the amplitudes in the KO I/R group were higher than in the WT I/R group. We observed retinal thinning in WT I/R mice after 3 and 7 days. Although compared to the KO CO group, retinal thinning was not observed in the KO I/R group until 7 days. The number of PKCα+ rod-bipolar cells, recoverin+ photoreceptor staining and Prkca and Rcvrn expression were comparable in all groups. However, reduced rhodopsin protein as well as Rho and Gnat1 mRNA expression levels of rod-photoreceptors were found in the WT I/R, but not in the KO I/R retina. Additionally, a lower number of activated caspase 3+ cells was observed in the KO I/R group. Finally, both ischemic groups displayed enhanced vesicular glutamate transporter 1 (vGlut1) levels. Collectively, KO mice showed diminished rod-photoreceptor degeneration and retinal dysfunction after I/R. Elevated vGlut1 levels after ischemia could be related to an impaired glutamatergic photoreceptor-bipolar cell signaling and excitotoxicity. Our study provides novel evidence that Tnc reinforces ischemic retinal degeneration, possibly by synaptic remodeling.

MALAT1 as a Versatile Regulator of Cancer: Overview of the updates from Predatory role as Competitive Endogenous RNA to Mechanistic In-sights

2020 ◽  
Vol 20 ◽  
Author(s):  
Ammad Ahmad Farooqi ◽  
Evangelia Legaki ◽  
Maria Gazouli ◽  
Silvia Rinaldi ◽  
Rossana Berardi
Keyword(s):  
Molecular Biology ◽  
Detailed Analysis ◽  
Signaling Pathways ◽  
Individualized Medicine ◽  
Signaling Cascades ◽  
Oncogenic Signaling ◽  
Non Coding Rnas ◽  
Oncogenic Signaling Pathways ◽  
Competitive Endogenous Rna

: Central dogma of molecular biology has remained cornerstone of classical molecular biology but serendipitous discovery of microRNAs (miRNAs) in nematodes paradigmatically shifted our current understanding of the intricate mech-anisms which occur during transitions from transcription to translation. Discovery of miRNA captured tremendous attention and appreciation and we had witnessed an explosion in the field of non-coding RNAs. Ground-breaking discoveries in the field of non-coding RNAs have helped in better characterization of microRNAs and long non-coding RNAs (LncRNAs). There is an ever-increasing list of miRNA targets which are regulated by MALAT1 to stimulate or repress expression of tar-get genes. However, in this review our main focus is to summarize mechanistic insights related to MALAT1-mediated regu-lation of oncogenic signaling pathways. We have discussed how MALAT1 modulated TGF/SMAD and Hippo pathways in various cancers. We have also comprehensively summarized how JAK/STAT and Wnt/β-catenin pathways stimulated MALAT1 expression and consequentially how MALAT1 potentiated these signaling cascades to promote cancer. MALAT1 research has undergone substantial broadening however, there is still a need to identify additional mechanisms. MALAT1 is involved in multi-layered regulation of multiple transduction cascades and detailed analysis of different pathways will be helpful in getting a step closer to individualized medicine.

scholarly journals Molecular Pathogenesis of Hodgkin Lymphoma: Past, Present, Future

2020 ◽  
Vol 21 (18) ◽  
pp. 6623 ◽  
Author(s):  
Marc Bienz ◽  
Salima Ramdani ◽  
Hans Knecht
Keyword(s):  
Immune System ◽  
Targeted Therapy ◽  
Signaling Pathways ◽  
Hodgkin Lymphoma ◽  
Genetic Instability ◽  
Host Immune System ◽  
Cellular Interactions ◽  
Classical Hodgkin Lymphoma ◽  
The Past

Our understanding of the tumorigenesis of classical Hodgkin lymphoma (cHL) and the formation of Reed–Sternberg cells (RS-cells) has evolved drastically in the last decades. More recently, a better characterization of the signaling pathways and the cellular interactions at play have paved the way for new targeted therapy in the hopes of improving outcomes. However, important gaps in knowledge remain that may hold the key for significant changes of paradigm in this lymphoma. Here, we discuss the past, present, and future of cHL, and review in detail the more recent discoveries pertaining to genetic instability, anti-apoptotic signaling pathways, the tumoral microenvironment, and host-immune system evasion in cHL.

scholarly journals Characterization of Liposomes Using Quantitative Phase Microscopy (QPM)

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 590
Author(s):  
Jennifer Cauzzo ◽  
Nikhil Jayakumar ◽  
Balpreet Singh Ahluwalia ◽  
Azeem Ahmad ◽  
Nataša Škalko-Basnet
Keyword(s):  
Rapid Development ◽  
Fluorescent Labeling ◽  
Label Free ◽  
Batch Mode ◽  
Full Field ◽  
Quantitative Phase ◽  
Phase Microscopy ◽  
Quantitative Phase Microscopy ◽  
Tracking Ability

The rapid development of nanomedicine and drug delivery systems calls for new and effective characterization techniques that can accurately characterize both the properties and the behavior of nanosystems. Standard methods such as dynamic light scattering (DLS) and fluorescent-based assays present challenges in terms of system’s instability, machine sensitivity, and loss of tracking ability, among others. In this study, we explore some of the downsides of batch-mode analyses and fluorescent labeling, while introducing quantitative phase microscopy (QPM) as a label-free complimentary characterization technique. Liposomes were used as a model nanocarrier for their therapeutic relevance and structural versatility. A successful immobilization of liposomes in a non-dried setup allowed for static imaging conditions in an off-axis phase microscope. Image reconstruction was then performed with a phase-shifting algorithm providing high spatial resolution. Our results show the potential of QPM to localize subdiffraction-limited liposomes, estimate their size, and track their integrity over time. Moreover, QPM full-field-of-view images enable the estimation of a single-particle-based size distribution, providing an alternative to the batch mode approach. QPM thus overcomes some of the drawbacks of the conventional methods, serving as a relevant complimentary technique in the characterization of nanosystems.

Single-Shot Full-Field Characterization of Short Pulses by Using Temporal Annealing Modified Gerchberg–Saxton Algorithm

2017 ◽  
Vol 35 (13) ◽  
pp. 2541-2547 ◽  
Author(s):  
Zhi Qiao ◽  
Yudong Yao ◽  
Xiaochao Wang ◽  
Wei Fan ◽  
Zunqi Lin
Keyword(s):  
Single Shot ◽  
Short Pulses ◽  
Full Field

scholarly journals Characterization of T Cells Specific for CFP-10 and ESAT-6 in Mycobacterium tuberculosis-Infected Mauritian Cynomolgus Macaques

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Amy Ellis ◽  
Alexis Balgeman ◽  
Mark Rodgers ◽  
Cassaundra Updike ◽  
Jaime Tomko ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Mhc Class Ii ◽  
Nonhuman Primates ◽  
Content Type ◽  
Host Immune Responses ◽  
Cell Responses ◽  
Cynomolgus Macaques ◽  
Mhc Haplotype

ABSTRACT Nonhuman primates can be used to study host immune responses to Mycobacterium tuberculosis. Mauritian cynomolgus macaques (MCMs) are a unique group of animals that have limited major histocompatibility complex (MHC) genetic diversity, such that MHC-identical animals can be infected with M. tuberculosis. Two MCMs homozygous for the relatively common M1 MHC haplotype were bronchoscopically infected with 41 CFU of the M. tuberculosis Erdman strain. Four other MCMs, which had at least one copy of the M1 MHC haplotype, were infected with a lower dose of 3 CFU M. tuberculosis. All animals mounted similar T-cell responses to CFP-10 and ESAT-6. Two epitopes in CFP-10 were characterized, and the MHC class II alleles restricting them were determined. A third epitope in CFP-10 was identified but exhibited promiscuous restriction. The CFP-10 and ESAT-6 antigenic regions targeted by T cells in MCMs were comparable to those seen in cases of human M. tuberculosis infection. Our data lay the foundation for generating tetrameric molecules to study epitope-specific CD4 T cells in M. tuberculosis-infected MCMs, which may guide future testing of tuberculosis vaccines in nonhuman primates.

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