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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 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Molecular and Cellular Characterization of a Zebrafish Optic Pathway Tumor Line Implicates Glia-Derived Progenitors in Tumorigenesis

In this study we describe the molecular and cellular characterization of a zebrafish mutant that develops tumors in the optic pathway. Heterozygous Tg(flk1:RFP)is18 transgenic adults develop tumors of the retina, optic nerve and optic tract. Molecular and genetic mapping demonstrate the tumor phenotype is linked to a high copy number transgene array integrated in the lincRNA gene lincRNAis18/ Zv9_00007276 on chromosome 3. TALENs were used to isolate a 147kb deletion allele that removes exons 2–5 of the lincRNAis18 gene. Deletion allele homozygotes are viable and do not develop tumors, indicating loss of function of the lincRNAis18 locus is not the trigger for tumor onset. Optic pathway tumors in the Tg(flk1:RFP)is18 mutant occur with a penetrance of 80–100% by 1 year of age. The retinal tumors are highly vascularized and composed of rosettes of various sizes embedded in a fibrous matrix. Immunohistochemical analysis showed increased expression of the glial markers GFAP and BLBP throughout retinal tumors and in dysplastic optic nerve. We performed transcriptome analysis of pre-tumorous retina and retinal tumor tissue and found changes in gene expression signatures of radial glia and astrocytes (slc1a3), activated glia (atf3, blbp, apoeb), proliferating neural progenitors (foxd3, nestin, cdh2, her9/hes1), and glioma markers (S100b, vim). The transcriptome also revealed activation of cAMP, Stat3 and Wnt signal transduction pathways. qRT-PCR confirmed .10-fold overexpression of the Wnt pathway components hbegfa, ascl1a, and insm1a. Together the data indicate Mu¨ ller glia and/or astrocyte-derived progenitors could contribute to the zebrafish Tg(flk1:RFP)is18 optic pathway tumors.

59 BASIC BIOLOGICAL SCIENCES↗
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 NTRS2017

Renin-Angiotensin System (RAS) in Hematopoietic Stem/Progenitor Cells (HS/PC) Predicts Vaso-Reparative Dysfunction and Progression of Diabetic Retinopathy (DR)

Purpose: We tested the hypothesis that loss of angiotensin converting enzyme 2 (ACE2) within diabetic HS/PCs (Hematopoietic Stem/Progenitor Cells) would be detrimental to HS/PC reparative function, and alter their ability to contribute to vascular remodeling in human subjects and rodent models of DR (Diabetic Retinopathy). Methods: Subjects (n52) were recruited as controls (n13) or diabetics (n39) with either no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR or proliferative DR (PDR). Fluorescein angiograms were analyzed using Vessel Generation Analysis (VESGEN) software in a cohort of subjects. CD34+ HS/PCs were isolated from peripheral blood. RAS (Renin-Angiotensin System) gene expression and migration was measured. Diabetic ACE2 knockout (KO)C57BL6-Ins2 (Akita) mice at 3, 6 and 9 months of diabetes were compared to age-matched controls. Bone marrow HS/PC populations were analyzed by flow cytometry and migration and proliferation studies performed. Results: ACE2 gene expression in human CD34+ cells from diabetics without DR was increased compared to controls (p0.0437). Mas receptor mRNA was also increased in diabetics without DR, but reduced with the onset of NPDR (p0.0002), suggesting a loss of compensation. DR was associated with CD34+ cell migratory dysfunction. By VESGEN analysis, vessel density measured by several confirming parameters in early NPDR (n3) was greater than in normal retina (n6) in both arteries and veins, which suggests active retinal remodeling. ACE2KO-Akita and Akita cohorts showed reduced retinal thickness by OCT (Optical Coherence Tomography) at 9 months of diabetes. Absence of ACE2 in 9-month Akita mice led to an accelerated increase in acellular capillaries compared to diabetic alone. Electroretinogram (ERG) in ACE2KO-Akita mice resulted in persistent deterioration of the neural retina. Reparative function studies showed that ACE2KO exacerbated diabetes-induced impairment of LK (Low Potassium) cell migration and proliferative functions as early as 3-month of diabetes (p0.0019). Conclusions: Retinopathy and adverse vascular remodeling in subjects with diabetes was associated with a loss of the protective arm of RAS in HS/PCs. Loss of ACE2 exacerbated vascular dysfunction in diabetic mice.

retina↗
DOE OSTI2022

Structural and functional analysis of the human cone‐rod homeobox transcription factor

Abstract The cone‐rod homeobox (CRX) protein is a critical K50 homeodomain transcription factor responsible for the differentiation and maintenance of photoreceptor neurons in the vertebrate retina. Mutant alleles in the human gene encoding CRX result in a variety of distinct blinding retinopathies, including retinitis pigmentosa, cone‐rod dystrophy, and Leber congenital amaurosis. Despite the success of using in vitro biochemistry, animal models, and genomics approaches to study this clinically relevant transcription factor over the past 25 years since its initial characterization, there are no high‐resolution structures in the published literature for the CRX protein. In this study, we use bioinformatic approaches and small‐angle X‐ray scattering (SAXS) structural analysis to further understand the biochemical complexity of the human CRX homeodomain (CRX‐HD). We find that the CRX‐HD is a compact, globular monomer in solution that can specifically bind functional cis‐regulatory elements encoded upstream of retina‐specific genes. This study presents the first structural analysis of CRX, paving the way for a new approach to studying the biochemistry of this protein and its disease‐causing mutant protein variants.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

2022 Prentice Award Lecture: Advancing Retinal Imaging and Visual Function in Patient Management and Disease Mechanisms

Patient-based research plays a key role in probing basic visual mechanisms. Less-well recognized is the role of patient-based retinal imaging and visual function studies in elucidating disease mechanisms, which are accelerated by advances in imaging and function techniques and are most powerful when combined with the results from histology and animal models. A patient's visual complaints can be one key to patient management, but human data are also key to understanding disease mechanisms. Unfortunately, pathological changes can be difficult to detect. Before advanced retinal imaging, the measurement of visual function indicated the presence of pathological changes that were undetectable with existing clinical examination. Over the past few decades, advances in retinal imaging have increasingly revealed the unseen. This has led to great strides in the management of many diseases, particularly diabetic retinopathy and macular edema, and age-related macular degeneration. It is likely widely accepted that patient-based research, as in clinical trials, led to such positive outcomes. Both visual function measures and advanced retinal imaging have clearly demonstrated differences among retinal diseases. Contrary to initial thinking, sight-threatening damage in diabetes occurs to the outer retina and not only to the inner retina. This has been clearly indicated in patient results but has only gradually entered the clinical classifications and understanding of disease etiology. There is strikingly different pathophysiology for age-related macular degeneration compared with photoreceptor and retinal pigment epithelial genetic defects, yet research models and even some treatments confuse these. It is important to recognize the role that patient-based research plays in probing basic visual mechanisms and elucidating disease mechanisms, combining these findings with the concepts from histology and animal models. Thus, this article combines sample instrumentation from my laboratory and progress in the fields of retinal imaging and visual function.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

SU-F-T-659: Nanoparticle-Aided Eye Plaque Radiotherapy

Purpose: Eye plaque brachytherapy is one of the approaches for radiotherapy treatment for ocular cancers: retinoblastoma and choroidal melanoma. This study, investigates the potential benefits of using gold nanoparticles to enhance therapeutic efficacy during eye plaque brachytherapy. Methods: The EYE PHYSICS Inc. Plaque Simulator program distributed by IsoAid, LLC, Port Richey, Florida was used. It is based on the superposition of dose contributions from individual seeds following the TG–43 formalism. Dose enhancement factor (DEF) values for feasible nanoparticle concentrations from previous studies was used to investigate the benefit of using nanoparticles to enhance dose to tumour or reduce dose to healthy tissue. The dose enhancement factor (DEF) represents the ratio of the dose deposited in tumour with nanoparticles divided by dose deposited in the tumour without nanoparticles. The investigation was done for I–125 and Pd–103 typical sources employed for eye plaque brachytherapy. The prescription dose used is 85 Gy. Results: Lower dose enhancement values were obtained for Pd–103. With DEF of 2 due to gold nanoparticles, critical structure doses reduce by a factor of 2. Optic disc dose is 6.69 Gy and 4.571 Gy, opposite retina dose is 4.064 and 2.484 Gy, lens dose is 12.66 Gy and 9.870 Gy, and fovea dose is 9.85 Gy and 7.275 Gy. With DEF of 3 due to gold nanoparticles, critical structure doses reduce by a factor of 3. Optic disc dose is 4.352 Gy and 2.975 Gy, opposite retina dose is 2.644 Gy and 1.618 Gy, lens dose is 8.322 Gy and 6.427 Gy, and fovea dose is 4.815 Gy and 4.737 Gy. Conclusion: The results of this research predict that using gold nanoparticles will lead to major sparing of dose to critical structures. The finding provides more impetus for the development of nanoparticle–aided brachytherapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

2-Aminoethyl Methylphosphonate, a Potent and Rapidly Acting Antagonist of GABA A -ρ1 Receptors

All three classes of receptors for the inhibitory neurotransmitter GABA (GABAR) are expressed in the retina. This study investigated roles of GABAR, especially GABA(C)R (GABA(A)-rho), in retinal signaling in vivo by studying effects on the mouse electroretinogram (ERG) of genetic deletion of GABA(C)R versus pharmacological blockade using receptor antagonists. Brief full-field flash ERGs were recorded from anesthetized GABA(C)R(-/-) mice, and WT C57BL/6 (B6) mice, before and after intravitreal injection of GABA(C)R antagonists, TPMPA, 3-APMPA, or the more recently developed 2-AEMP; GABA(A)R antagonist, SR95531; GABA(B)R antagonist, CGP, and agonist, baclofen. Intravitreal injections of TPMPA and SR95531 were also made in Brown Norway rats. The effect of 2-AEMP on GABA-induced current was tested directly in isolated rat rod bipolar cells, and 2-AEMP was found to preferentially block GABA(C)R in those cells. Maximum amplitudes of dark (DA) and light-adapted (LA) ERG b-waves were reduced in GABA(C)R(-/-) mice, compared to B6 mice, by 30-60%; a-waves were unaltered and oscillatory potential amplitudes were increased. In B6 mice, after injection of TPMPA (also in rats), 3-APMPA or 2-AEMP, ERGs became similar to ERGs of GABA(C)R(-/-) mice. Blockade of GABA(A)Rs and GABA(B)Rs, or agonism of GABA(B)Rs did not alter B6 DA b-wave amplitude. The negative scotopic threshold response (nSTR) was slightly less sensitive in GABA(C)R(-/-) than in B6 mice, and unaltered by 2-AEMP. However, amplitudes of nSTR and photopic negative response (PhNR), both of which originate from inner retina, were enhanced by TPMPA and 3-APMPA, each of which has GABA(B) agonist properties, and further increased by baclofen. The finding that genetic deletion of GABA(C)R, the GABA(C)R antagonist 2-AEMP, and other antagonists all reduced ERG b-wave amplitude, supports a role for CABA(C)R in determining the maximum response amplitude of bipolar cells contributing to the b-wave. GABA(C)R antagonists differed in their effects on nSTR and PhNR; antagonists with GABA(B) agonist properties enhanced light-driven responses whereas 2-AEMP did not.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

A distal 594 bp ECR specifies Hmx1 expression in pinna and lateral facial morphogenesis and is regulated by the Hox-Pbx-Meis complex

Hmx1 encodes a homeodomain transcription factor expressed in the developing lateral craniofacial mesenchyme, retina and sensory ganglia. Mutation or mis-regulation of Hmx1 underlies malformations of the eye and external ear in multiple species. Deletion or insertional duplication of an evolutionarily conserved region (ECR) downstream of Hmx1 has recently been described in rat and cow, respectively. Here, we demonstrate that the impact of Hmx1 loss is greater than previously appreciated, with a variety of lateral cranioskeletal defects, auriculofacial nerve deficits, and duplication of the caudal region of the external ear. Using a transgenic approach, we demonstrate that a 594 bp sequence encompassing the ECR recapitulates specific aspects of the endogenous Hmx1 lateral facial expression pattern. Moreover, we show that Hoxa2, Meis and Pbx proteins act cooperatively on the ECR, via a core 32 bp sequence, to regulate Hmx1 expression. In conclusion, these studies highlight the conserved role for Hmx1 in BA2-derived tissues and provide an entry point for improved understanding of the causes of the frequent lateral facial birth defects in humans.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Cadmium-Free QD Building Blocks for Human Centric Lighting

This project developed Cd-free quantum dot (QD) downconverters for efficacious human-centric lighting (HCL) light emitting diode (LED) devices. Solid state HCL devices address the lack of light in the cyan wavelength region (460-490 nm) in white LEDs by enhancing the melanopic daylight efficacy ratio (MDER) value. MDER is a metric that indicates the degree to which artificial lighting stimulates nonvisual biological processes in the retina responsible for regulating circadian rhythms compared with natural lighting. The peak sensitivity of melanopsin in the retina is at 479 nm, therefore artificial lighting which can fill the well-known “cyan gap” may improve human health. Due to the Restriction of Hazardous Substances (RoHS) regulations, cadmium-free core/shell/shell QDs are the primary targets for low toxicity, tunable downconverters. Cyan- and red-emitting core/shell/shell QDs were implemented in LED devices toward achieving a brightness of 210 lm/W at 4000 K, CRI 90, and MDER > 0.7. Synthetic development of Cd-free materials yielded cyan InP/ZnS QDs with a photoluminescence quantum yield (PLQY) of ~60% between 480-490 nm, and red InP/ZnSe/(ZnSeS)/ZnS QDs reaching ~80% PLQY at 620-630 nm. We successfully demonstrated that the inclusion of cyan QDs increased the MDER value to ≥0.7, but the brightness of the HCL LED devices was hindered due to low PLQY values. However, upon substitution of the Cd-free cyan QD with a low-Cd QD with >90% PLQY, brightness improved by 25% over the Cd-free device to 179 lm/W. Despite the technical obstacles remaining toward improving emission characteristics and stability of QDs under high flux, we have confirmed the promise of narrow, tunable QD emitters in SSL packages toward the goal of healthy, human-centric lighting.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
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↗
NASA NTRS1966

Sensory, Decision and Control Systems: April to July 1966

The quarter reported here for the NASA contract, and the longer period reported for the Air Force contract, saw the development of two system concepts for the transmission of video data from a remote location to Earth. In the simpler system, a stereoscopic outline together with other data such as reflectance and possibly the texture of objects will be transmitted to Earth. The objects considered are those larger than a predetermined size and within a predetermined range. From the stereoscopic outlines presented to the operator on Earth he will decide what objects he would like pictured in full TV frames and order these transmitted. In the more elaborate system, TV cameras will be carried on a vehicle and the direction in which the vehicle moves will be chosen by an onboard decision computer. Perceptual decisions may also be made to identify objects whose characteristics have been reported to Earth and whose value to the Earth observer has been communicated back to the perceptual computer. The assembly of cameras, perceptual computer, decision computer and vehicle is called a robot. Photosensors for this robot are television cameras, the first models of which have been tested under computer control. A model of both the perceptual computer and the decision computer has been simulated. It consists of 12 modules, each of which makes an initial guess as to what the response to incoming data should be. Each takes the data from all other modules and combines it in a nonlinear fashion with the data coming directly into it to arrive at a mixed guess as to what act should be performed. When 60% of the modules vote 0. 5 probability for one act, that act is performed. Convergence to a satisfactory decision took from 5 to 25 time steps. The model of the frog's retina previously reported is here extended to that part of the brain, called the tectum, where the frog begins to respond to objects detected by the retina.

Control system↗
NASA NTRS1970

Automatic optometer operates with infrared test pattern

Refractive strength of human eye is monitored by optometer that automatically and continuously images infrared test pattern onto the retina. Condition of focus of the eye at any instant is determined from optometer settings needed to maintain focus of the pattern on the retina.

Cornsweet, T. N.↗
NASA NTRS1972

Human visual response to nuclear particle exposures

Experiments with accelerated helium ions were performed in an effort to localize the site of initial radiation interactions in the eye that lead to light flash observations by astronauts during spaceflight. The character and efficiency of helium ion induction of visual sensations depended on the state of dark adaptation of the retina; also, the same events were seen with different efficiencies and details when particle flux density changed. It was concluded that fast particles cause interactions in the retina, particularly in the receptor layer, and thus give rise to the sensations of light flashes, streaks, and supernovae.

Tobias, C. A.↗
NASA NTRS1974

System and method for character recognition

A character recognition system is disclosed in which each character in a retina, defining a scanning raster, is scanned with random lines uniformly distributed over the retina. For each type of character to be recognized the system stores a probability density function (PDF) of the random line intersection lengths and/or a PDF of the random line number of intersections. As an unknown character is scanned, the random line intersection lengths and/or the random line number of intersections are accumulated and based on a comparison with the prestored PDFs a classification of the unknown character is performed.

Hong, J. P.↗
NASA NTRS1985

Photographic Screening for Eye Defects

Images of retinas examined for characteristic patterns. Color photographs of retinas taken. Proper alinement of eye obtained by asking subject to gaze at light-emitting diode. "Red-eye" patterns in resulting color photographs examined by trained observers for signs of ocular defects. System used to check power of contact lenses and eyeglasses by taking photographs with these items in place.

Richardson, J.↗
NASA NTRS1985

Generation-V dual-Purkinje-image eyetracker

Major advances characterize the Generation-V dual-Purkinje-image eyetracker compared with the Generation-III version previously described. These advances include a large reduction in size, major improvements in frequency response and noise level, automatic alignment to a subject, and automatic adjustment for different separation between the visual and optic axes, which can vary considerably from subject to subject. In a number of applications described in the paper, the eyetracker is coupled with other highly specialized optical devices. These applications include accurately stabilizing an image on a subject's retina; accurately simulating a visually dead retinal region (i.e., a scotoma) of arbitrary shape, size, and position; and, for clinical purposes, stabilizing the position of a laser coagulator beam on a patient's retina so that the point of contact is unaffected by the patient's own eye movements.

Crane, H. D.↗
NASA NTRS1986

Optical correlator use at Johnson Space Center

For automation and robotics in the Space Station era, NASA's Johnson Space Center is pursuing several means of synthetic vision. The optical correlator is one such means. The deformable mirror device will form the basis of the first correlator in this project. In-house and contracted effort is being used. Initial in-house activities will concentrate on an impulse deconvolution technique and on a programmable retina for spatial remappings of an image prior to correlation. The retina will permit a form of edge extraction and other primitive operations. Additionally, it will be used as a research tool for assisting persons with low vision.

Juday, Richard D.↗
NASA NTRS1991

Spatial vision within egocentric and exocentric frames of reference

It is remarkable that we are able to perceive a stable visual world and judge the directions, orientations, and movements of visual objects given that images move on the retina, the eyes move in the head, the head moves on the body, and the body moves in space. An understanding of the mechanisms underlying perceptual stability and spatial judgements requires precise definitions of relevant coordinate systems. An egocentric frame of reference is defined with respect to some part of the observer. There are four principal egocentric frames of reference, a station-point frame associated with the nodal point of the eye, an retinocentric frame associated with the retina, a headcentric frame associated with the head, and a bodycentric frame (torsocentric) associated with the torso. Additional egocentric frames can be identified with respect to any segment of the body. An egocentric task is one in which the position, orientation, or motion of an object is judged with respect to an egocentric frame of reference. A proprioceptive is a special kind of egocentric task in which the object being judged is also part of the body. An example of a proprioceptive task is that of directing the gaze toward the seen or unseen toe. An exocentric frame of reference is external to the observer. Geographical coordinates and the direction of gravity are examples of exocentric frames of reference. These various frames are listed in tabular form, together with examples of judgements of each type.

Howard, Ian P.↗