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Results for “retinal ganglion cells”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2003

Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: bifurcation and melanopsin immunoreactivity

The circadian clock in the suprachiasmatic nucleus (SCN) receives direct retinal input via the retinohypothalamic tract (RHT), and the retinal ganglion cells contributing to this projection may be specialized with respect to direct regulation of the circadian clock. However, some ganglion cells forming the RHT bifurcate, sending axon collaterals to the intergeniculate leaflet (IGL) through which light has secondary access to the circadian clock. The present studies provide a more extensive examination of ganglion cell bifurcation and evaluate whether ganglion cells projecting to several subcortical visual nuclei contain melanopsin, a putative ganglion cell photopigment. The results showed that retinal ganglion cells projecting to the SCN send collaterals to the IGL, olivary pretectal nucleus, and superior colliculus, among other places. Melanopsin-immunoreactive (IR) ganglion cells are present in the hamster retina, and some of these cells project to the SCN, IGL, olivary pretectal nucleus, or superior colliculus. Triple-label analysis showed that melanopsin-IR cells bifurcate and project bilaterally to each SCN, but not to the other visual nuclei evaluated. The melanopsin-IR cells have photoreceptive characteristics optimal for circadian rhythm regulation. However, the presence of moderately widespread bifurcation among ganglion cells projecting to the SCN, and projection by melanopsin-IR cells to locations distinct from the SCN and without known rhythm function, suggest that this ganglion cell type is generalized, rather than specialized, with respect to the conveyance of photic information to the brain. Copyright 2003 Wiley-Liss, Inc.

NASA Discipline Neuroscience↗
DOE OSTI2022

Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types

The genesis of broad neuronal classes from multipotential neural progenitor cells has been extensively studied, but less is known about the diversification of a single neuronal class into multiple types. We used single-cell RNA-seq to study how newly born (postmitotic) mouse retinal ganglion cell (RGC) precursors diversify into ~45 discrete types. Computational analysis provides evidence that RGC transcriptomic type identity is not specified at mitotic exit, but acquired by gradual, asynchronous restriction of postmitotic multipotential precursors. Some types are not identifiable until a week after they are generated. Immature RGCs may be specified to project ipsilaterally or contralaterally to the rest of the brain before their type identity emerges. Optimal transport inference identifies groups of RGC precursors with largely nonoverlapping fates, distinguished by selectively expressed transcription factors that could act as fate determinants. Our study provides a framework for investigating the molecular diversification of discrete types within a neuronal class.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Evolution of neuronal cell classes and types in the vertebrate retina

The basic plan of the retina is conserved across vertebrates, yet species differ profoundly in their visual needs1. Retinal cell types may have evolved to accommodate these varied needs, but this has not been systematically studied. Here we generated and integrated single-cell transcriptomic atlases of the retina from 17 species: humans, two non-human primates, four rodents, three ungulates, opossum, ferret, tree shrew, a bird, a reptile, a teleost fish and a lamprey. We found high molecular conservation of the six retinal cell classes (photoreceptors, horizontal cells, bipolar cells, amacrine cells, retinal ganglion cells (RGCs) and Müller glia), with transcriptomic variation across species related to evolutionary distance. Major subclasses were also conserved, whereas variation among cell types within classes or subclasses was more pronounced. However, an integrative analysis revealed that numerous cell types are shared across species, based on conserved gene expression programmes that are likely to trace back to an early ancestral vertebrate. The degree of variation among cell types increased from the outer retina (photoreceptors) to the inner retina (RGCs), suggesting that evolution acts preferentially to shape the retinal output. Finally, we identified rodent orthologues of midget RGCs, which comprise more than 80% of RGCs in the human retina, subserve high-acuity vision, and were previously believed to be restricted to primates. By contrast, the mouse orthologues have large receptive fields and comprise around 2% of mouse RGCs. Projections of both primate and mouse orthologous types are overrepresented in the thalamus, which supplies the primary visual cortex. We suggest that midget RGCs are not primate innovations, but are descendants of evolutionarily ancient types that decreased in size and increased in number as primates evolved, thereby facilitating high visual acuity and increased cortical processing of visual information.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2011

Molecular Mechanisms of Circadian Regulation During Spaceflight

Disruption of the regular environmental circadian cues in addition to stringent and demanding operational schedules are two main factors that undoubtedly impact sleep patterns and vigilant performance in the astronaut crews during spaceflight. Most research is focused on the behavioral aspects of the risk of circadian desynchronization, characterized by fatigue and health and performance decrement. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate this risk. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. The molecular clock consists of sets of proteins that perform different functions within the clock machinery: circadian oscillators (genes whose expression levels cycle during the day, keep the pass of cellular time and regulate downstream effector genes), the effector or output genes (those which impact the physiology of the tissue or organism), and the input genes (responsible for sensing the environmental cues that allow circadian entrainment). The main environmental cue is light. As opposed to the known photoreceptors (rods and cones), the non-visual light stimulus is received by a subset of the population of retinal ganglion cells called intrinsically photosensitive retinal ganglion cells (ipRGC) that express melanopsin (opsin 4 -Opn4-) as the photoreceptor. We hypothesize that spaceflight may affect ipRGC and melanopsin expression, which may be a contributing cause of circadian disruption during spaceflight. To answer this question, eyes from albino Balb/cJ mice aboard STS-133 were collected for histological analysis and gene expression profiling of the retina at 1 and 7 days after landing. Both vivarium and AEM (animal enclosure module) mice were used as ground controls. Opn4 expression was analyzed by real time RT/qPCR and retinal sections were stained for Opn4 immunofluorescence. Opn4 was decreased (abrogated in one case) in retinas that concurrently showed higher evidence of oxidative stress. We propose that oxidative stress can lead to a decrease in melanopsin expression, likely via ipRGC loss or impairment, and thus, it can be a contributing factor to circadian disruption during spaceflight. Countermeasures contemplating the use of light should therefore be complemented with melanopsin expression maintenance and/or reduction in oxidative stress.

Zanello, Susana↗
NASA NTRS1989

A hexagonal orthogonal-oriented pyramid as a model of image representation in visual cortex

Retinal ganglion cells represent the visual image with a spatial code, in which each cell conveys information about a small region in the image. In contrast, cells of the primary visual cortex use a hybrid space-frequency code in which each cell conveys information about a region that is local in space, spatial frequency, and orientation. A mathematical model for this transformation is described. The hexagonal orthogonal-oriented quadrature pyramid (HOP) transform, which operates on a hexagonal input lattice, uses basis functions that are orthogonal, self-similar, and localized in space, spatial frequency, orientation, and phase. The basis functions, which are generated from seven basic types through a recursive process, form an image code of the pyramid type. The seven basis functions, six bandpass and one low-pass, occupy a point and a hexagon of six nearest neighbors on a hexagonal lattice. The six bandpass basis functions consist of three with even symmetry, and three with odd symmetry. At the lowest level, the inputs are image samples. At each higher level, the input lattice is provided by the low-pass coefficients computed at the previous level. At each level, the output is subsampled in such a way as to yield a new hexagonal lattice with a spacing square root of 7 larger than the previous level, so that the number of coefficients is reduced by a factor of seven at each level. In the biological model, the input lattice is the retinal ganglion cell array. The resulting scheme provides a compact, efficient code of the image and generates receptive fields that resemble those of the primary visual cortex.

Watson, Andrew B.↗
DOE OSTI2023

Retinal microvascular and neuronal pathologies probed in vivo by adaptive optical two-photon fluorescence microscopy

The retina, behind the transparent optics of the eye, is the only neural tissue whose physiology and pathology can be non-invasively probed by optical microscopy. The aberrations intrinsic to the mouse eye, however, prevent high-resolution investigation of retinal structure and function in vivo. Optimizing the design of a two-photon fluorescence microscope (2PFM) and sample preparation procedure, we found that adaptive optics (AO), by measuring and correcting ocular aberrations, is essential for resolving putative synaptic structures and achieving three-dimensional cellular resolution in the mouse retina in vivo. Applying AO-2PFM to longitudinal retinal imaging in transgenic models of retinal pathology, we characterized microvascular lesions with sub-capillary details in a proliferative vascular retinopathy model, and found Lidocaine to effectively suppress retinal ganglion cell hyperactivity in a retinal degeneration model. Tracking structural and functional changes at high-resolution longitudinally, AO-2PFM enables microscopic investigations of retinal pathology and pharmacology for disease diagnosis and treatment in vivo.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Gap junctions fine-tune ganglion cell signals to equalize response kinetics within a given electrically coupled array

Retinal ganglion cells (RGCs) summate inputs and forward a spike train code to the brain in the form of either maintained spiking (sustained) or a quickly decaying brief spike burst (transient). We report diverse response transience values across the RGC population and, contrary to the conventional transient/sustained scheme, responses with intermediary characteristics are the most abundant. Pharmacological tests showed that besides GABAergic inhibition, gap junction (GJ)–mediated excitation also plays a pivotal role in shaping response transience and thus visual coding. More precisely GJs connecting RGCs to nearby amacrine and RGCs play a defining role in the process. These GJs equalize kinetic features, including the response transience of transient OFF alpha (tOFFα) RGCs across a coupled array. We propose that GJs in other coupled neuron ensembles in the brain are also critical in the harmonization of response kinetics to enhance the population code and suit a corresponding task.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Differential Accumulation of Misfolded Prion Strains in Natural Hosts of Prion Diseases

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of neurodegenerative protein misfolding diseases that invariably cause death. TSEs occur when the endogenous cellular prion protein (PrP C ) misfolds to form the pathological prion protein (PrP Sc ), which templates further conversion of PrP C to PrP Sc , accumulates, and initiates a cascade of pathologic processes in cells and tissues. Different strains of prion disease within a species are thought to arise from the differential misfolding of the prion protein and have different clinical phenotypes. Different strains of prion disease may also result in differential accumulation of PrP Sc in brain regions and tissues of natural hosts. Here, we review differential accumulation that occurs in the retinal ganglion cells, cerebellar cortex and white matter, and plexuses of the enteric nervous system in cattle with bovine spongiform encephalopathy, sheep and goats with scrapie, cervids with chronic wasting disease, and humans with prion diseases. By characterizing TSEs in their natural host, we can better understand the pathogenesis of different prion strains. This information is valuable in the pursuit of evaluating and discovering potential biomarkers and therapeutics for prion diseases.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2002

Spatiotemporal features of early neuronogenesis differ in wild-type and albino mouse retina

In albino mammals, lack of pigment in the retinal pigment epithelium is associated with retinal defects, including poor visual acuity from a photoreceptor deficit in the central retina and poor depth perception from a decrease in ipsilaterally projecting retinal fibers. Possible contributors to these abnormalities are reported delays in neuronogenesis (Ilia and Jeffery, 1996) and retinal maturation (Webster and Rowe, 1991). To further determine possible perturbations in neuronogenesis and/or differentiation, we used cell-specific markers and refined birth dating methods to examine these events during retinal ganglion cell (RGC) genesis in albino and pigmented mice from embryonic day 11 (E11) to E18. Our data indicate that relative to pigmented mice, more ganglion cells are born in the early stages of neuronogenesis in the albino retina, although the initiation of RGC genesis in the albino is unchanged. The cellular organization of the albino retina is perturbed as early as E12. In addition, cell cycle kinetics and output along the nasotemporal axis differ in retinas of albino and pigmented mice, both absolutely, with the temporal aspect of the retina expanded in albino, and relative to the position of the optic nerve head. Finally, blocking melanin synthesis in pigmented eyecups in culture leads to an increase in RGC differentiation, consistent with a role for melanin formation in regulating RGC neuronogenesis. These results point to spatiotemporal defects in neuronal production in the albino retina, which could perturb expression of genes that specify cell fate, number, and/or projection phenotype.

NASA Discipline Developmental Biology↗
DOE OSTI2021

Protective effects of intravitreal administration of mesenchymal stem cell-derived exosomes in an experimental model of optic nerve injury

Traumatic optic neuropathy results in the loss of retinal ganglion cells (RGCs), leading to unavoidable visual impairment. However, there is no effective therapy by far. Accumulated studies support the perception that mesenchymal stem cells (MSCs) secrete exosomes that serve as a protective paracrine factor. The study aimed to explore and evaluate the potential therapeutic effects of intravitreal transplantation of MSC-derived exosomes (MSC-exos) in an experimental model of optic nerve crush (ONC). Exosomes were isolated from rat MSCs and characterized by transmission electron microscope and western blotting. At the onset of ONC, a single intravitreal injection of exosomes or PBS was administered to the rats. At day 30, hematoxylin and eosin staining, immunohistochemistry, and βIII-tubulin staining were performed to evaluate the survival of RGCs. Moreover, TUNEL assay was used to examine the apoptosis of RGCs. Inflammation-relevant factors were identified via quantitative polymerase chain reaction. The expression levels of cell apoptosis-related molecules and key members of the PI3K/AKT signaling pathway were determined via western blot analysis. We found that MSC-exos exhibited typical characteristic morphologies (cup-shaped) and sizes (peak size of 93 nm). Furthermore, they exhibited substantial expression of the exosome markers CD63 and TSG101, but lacked the expression of the cellular marker GM130. Treatment with intravitreal MSC-exos notably promoted the survival of RGCs in ONC rats. The level of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, IL-8, and MCP-1, were reduced, whereas those of the anti-inflammatory factor IL-10 were increased. Moreover, the apoptosis induced by ONC was decreased by the administration of MSC-exos via upregulation of the Bcl-2/Bax ratio and downregulation of caspase-3 activity. Furthermore, MSC-exos significantly stimulated AKT phosphorylation, whereas LY294002 restored the apoptosis-preventing effects of MSC-exos. The results of our results demonstrated that intravitreal administration of MSC-exos ameliorates ONC-induced injury in a rat model. These findings might aid in the development of effective exosome-based therapeutic strategies for the treatment of optic nerve degeneration.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2017

Circadian and Fatigue Effects on the Dynamics of the Pupillary Light Reflex

The pupillary light reflex (PLR) is known to be driven by the photo-entrainment of intrinsically-photosensitive retinal ganglion cells. These ganglion cells are known to have retino-hypothalamic projections to the suprachiasmatic nuclei (SCN), which regulates circadian rhythms, and bilateral retinal projections to the pretectal area, which mediates the PLR (Dacey et al., 2005; Hattar et al., 2002, 2006). The magnitude of the PLR has previously been shown to show circadian variation (Mnch et al., 2012). In this study, we used a constant routine protocol (Mills et al., 1978) to examine circadian and fatigue effects on the dynamics of the PLR. We characterized the PLR (pupil size as a function of time) in response to a square-wave change in the luminance of a white display background, at ten different times over a single circadian cycle. Twelve subjects participated in three daytime baseline runs followed by 7 nighttime runs each separated by an hour (17 23 hours after awakening). The constriction and dilation phases of the PLR waveform were fit separately with a single exponential model (Longtin Milton, 1988; Milton Longtin, 1990) with time constants estimated using a least-squares method. The dilation time constant exhibited a distinct sinusoidal modulation across the circadian cycle and, after 23 hours of wakefulness, decreased on average by 82 ms (paired t-test, p 0.05) relative to baseline (mean: 543 ms). The constriction time constant however, did not show an overall decrease with increased wakefulness. We conclude that the dynamics of the PLR show circadian variation and that, in addition, the briskness of the dilation response to a step-decrease in luminance shows a homeostatic enhancement with increased wakefulness.

human performance↗
DOE OSTI2022

Transience of the Retinal Output Is Determined by a Great Variety of Circuit Elements

Retinal ganglion cells (RGCs) encrypt stimulus features of the visual scene in action potentials and convey them toward higher visual centers in the brain. Although there are many visual features to encode, our recent understanding is that the ~46 different functional subtypes of RGCs in the retina share this task. In this scheme, each RGC subtype establishes a separate, parallel signaling route for a specific visual feature (e.g., contrast, the direction of motion, luminosity), through which information is conveyed. The efficiency of encoding depends on several factors, including signal strength, adaptational levels, and the actual efficacy of the underlying retinal microcircuits. Upon collecting inputs across their respective receptive field, RGCs perform further analysis (e.g., summation, subtraction, weighting) before they generate the final output spike train, which itself is characterized by multiple different features, such as the number of spikes, the inter-spike intervals, response delay, and the rundown time (transience) of the response. These specific kinetic features are essential for target postsynaptic neurons in the brain in order to effectively decode and interpret signals, thereby forming visual perception. We review recent knowledge regarding circuit elements of the mammalian retina that participate in shaping RGC response transience for optimal visual signaling.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2012

Effects of Dietary Iron and Gamma Radiation on the Rat Retina

A health risk of concern for NASA relates to radiation exposure and its synergistic effects with other space environmental factors, includi ng nutritional status of the crew. Astronauts consume almost three times the recommended daily allowance of iron due to the use of fortifie d foods aboard the International Space Station, with iron intake occa sionally exceeding six times the recommended values. Recently, NASA has become concerned with visual changes associated with spaceflight, a nd research is being conducted to elucidate the etiology of eye structure alterations in the spaceflight environment. Terrestrially, iron o verload is also associated with certain optic neuropathies. In additi on, due to its role in Fenton reactions, iron can potentiate oxidative stress, which is a recognized cause of cataract formation. As part o f a study investigating the combined effects of radiation exposure an d iron overload on multiple physiological systems, we focused on defining the effects of both treatments on eye biology. In this study, 12- week-old Sprague-Dawley rats were assigned to one of four experimental groups: normal iron/no radiation (Control/Sham), high iron/no radiat ion (Fe/Sham), normal iron/gamma radiation (3 Gy cumulative dose, fra ctionated at 0.375 Gy/d every other day for 16 d) (Control/Rad), and high iron/gamma radiation (Fe/Rad). Oxidative stress-induced DNA damag e, measured as concentration of the marker 8-hydroxy-2'-deoxyguanosine (8OHdG) in eye retinal tissue by enzyme-immunoanalysis did not show significant changes among treatments. However, there was an overall i ncrease in 8OHdG immunostaining density in retina sections due to radiation exposure (P = 0.05). Increased dietary iron and radiation expos ure had an interactive effect (P = 0.02) on 8OHdG immunostaining of t he retinal ganglion cell layer with iron diet increasing the signal in the group not exposed to radiation (P = 0.05). qPCR gene expression profiling of relevant target genes indicated upregulation of ferritin light chain (P = 0.09) as a result of dietary iron but no change in e xpression of the gene for ferritin heavy chain. Immunolocalization of light chain and heavy chain of the iron storage protein ferritin showed the expected distribution in the choroid, photoreceptor layer, inn er nuclear layer and in the inner plexiform layer that corresponded t o the synaptic terminals of bipolar cells. Evidence of stress and damage in the retina was also suggested by a decrease in expression of th e survival marker Bcl2 (P = 0.01) and the protective proteins clusterin (P = 0.04) and heat shock factor 1 (Hsf1, P < 0.001), as a result o f increased dietary iron. The effect of increased iron on expression of the antioxidant enzyme heme oxygenase 1 (Hmox1) had a significant interaction with the effect of radiation (P < 0.001). In summary, the results of this study indicate that both gamma radiation exposure and a moderate increase in dietary iron can contribute to deleterious cha nges in retinal health and physiology.

Morgan, Jennifer↗
DOE OSTI2024

Light: An Extrinsic Factor Influencing Animal-based Research

Abstract Light is an environmental factor that is extrinsic to animals themselves and that exerts a profound influence on the regulation of circadian, neurohormonal, metabolic, and neurobehavioral systems of all animals, including research animals. These widespread biologic effects of light are mediated by distinct photoreceptors—rods and cones that comprise the conventional visual system and melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) of the nonvisual system that interact with the rods and cones. The rods and cones of the visual system, along with the ipRGCs of the nonvisual system, are species distinct in terms of opsins and opsin concentrations and interact with one another to provide vision and regulate circadian rhythms of neurohormonal and neurobehavioral responses to light. Here, we review a brief history of lighting technologies, the nature of light and circadian rhythms, our present understanding of mammalian photoreception, and current industry practices and standards. We also consider the implications of light for vivarium measurement, production, and technological application and provide simple recommendations on artificial lighting for use by regulatory authorities, lighting manufacturers, designers, engineers, researchers, and research animal care staff that ensure best practices for optimizing animal health and well-being and, ultimately, improving scientific outcomes.

Veterinary Sciences↗
NASA NTRS2005

Photons, clocks, and consciousness

Light profoundly impacts human consciousness through the stimulation of the visual system and powerfully regulates the human circadian system, which, in turn, has a broad regulatory impact on virtually all tissues in the body. For more than 25 years, the techniques of action spectroscopy have yielded insights into the wavelength sensitivity of circadian input in humans and other mammalian species. The seminal discovery of melanopsin, the photopigment in intrinsically photosensitive retinal ganglion cells, has provided a significant turning point for understanding human circadian phototransduction. Action spectra in humans show that the peak wavelength sensitivity for this newly discovered sensory system is within the blue portion of the spectrum. This is fundamentally different from the three-cone photopic visual system, as well as the individual rod and cone photoreceptor peaks. Studies on rodents, nonhuman primates, and humans indicate that despite having a different wavelength fingerprint, these classic visual photoreceptors still provide an element of input to the circadian system. These findings open the door to innovations in light therapy for circadian and affective disorders, as well as possible architectural light applications.

Review↗
NASA NTRS2017

User-Wearable Devices that Monitor Exposure to Blue Light and Recommend Adjustments Thereto

Described herein are user-wearable devices that include an optical sensor, and methods for use therewith. In certain embodiments, an optical sensor of a user-wearable device (e.g., a wrist-worn device) is used to detect blue light that is incident on the optical sensor and to produce a blue light detection signal indicative thereof, and thus, indicative of the response of the user's intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). In dependence on the blue light detection signal, there is a determination of a metric indicative of an amount of blue light detected by the optical sensor. The metric is compared to a corresponding threshold, and a user notification is triggered in dependence on results of the comparing, wherein the user notification informs a person wearing the user-wearable device to adjust their exposure to light.

Lee, Yong Jin↗