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https://www.readbyqxmd.com/read/29792886/t-grasp-a-targeted-grasp-for-assessing-neuronal-connectivity
#1
Harold K Shearin, Casey D Quinn, Robert D Mackin, Ian S Macdonald, R Steven Stowers
BACKGROUND: Understanding how behaviors are generated by neural circuits requires knowledge of the synaptic connections between the composite neurons. Methods for mapping synaptic connections, such as electron microscopy and paired recordings, are labor intensive and alternative methods are thus desirable. NEW METHOD: Development of a targeted GFP Reconstitution Across Synaptic Partners(GRASP) method, t-GRASP, for assessing neural connectivity is described. RESULTS: Numerous different pre-synaptic and post-synaptic/dendritic proteins were tested for enhancing the specificity of GRASP signal to synaptic regions...
May 21, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29791852/melanopsin-retinal-ganglion-cells-regulate-cone-photoreceptor-lamination-in-the-mouse-retina
#2
Adele R Tufford, Jessica R Onyak, Katelyn B Sondereker, Jasmine A Lucas, Aaron M Earley, Pierre Mattar, Samer Hattar, Tiffany M Schmidt, Jordan M Renna, Michel Cayouette
Newborn neurons follow molecular cues to reach their final destination, but whether early life experience influences lamination remains largely unexplored. As light is among the first stimuli to reach the developing nervous system via intrinsically photosensitive retinal ganglion cells (ipRGCs), we asked whether ipRGCs could affect lamination in the developing mouse retina. We show here that ablation of ipRGCs causes cone photoreceptors to mislocalize at different apicobasal positions in the retina. This effect is partly mediated by light-evoked activity in ipRGCs, as dark rearing or silencing of ipRGCs leads a subset of cones to mislocalize...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29789660/multicolor-tm-imaging-in-combined-hamartoma-of-the-retina-and-retinal-pigment-epithelium
#3
Konstantinos Kaprinis, Hannaa Bobat, Gabriella De Salvo
PURPOSE: To describe the principle characteristics of combined hamartoma of the retina and retinal pigment epithelium ('combined harmatoma') on MultiColorTM imaging and evaluate its role as a diagnostic and management tool. METHODS: Retrospective, observational case series comprising three patients with unilateral, juxtapapillary combined harmatoma. Complete ophthalmic examination was performed. MultiColorTM , including green reflectance (GR) and near infra-red reflectance (NIRR), optical coherence tomography (OCT) and autofluorescence (AF) imaging were obtained (Heidelberg Spectralis)...
May 23, 2018: Eye
https://www.readbyqxmd.com/read/29789402/rod-specific-ablation-using-the-nitroreductase-metronidazole-system-to-investigate-regeneration-in-xenopus
#4
Reyna I Martinez-De Luna, Michael E Zuber
Genetically controlled cell type-specific ablation provides a reproducible method to induce regeneration that can be temporally and spatially controlled. Until recently, regeneration studies in Xenopus have relied on surgical methods to stimulate regeneration. These methods are labor intensive and not as reproducible as a genetically controlled approach. In this protocol we describe selective ablation of rod photoreceptors in the premetamorphic Xenopus laevis retina using the nitroreductase/metronidazole (NTR/Mtz) system...
May 22, 2018: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/29789384/mutations-in-eid1-and-lnk2-caused-light-conditional-clock-deceleration-during-tomato-domestication
#5
Niels A Müller, Lei Zhang, Maarten Koornneef, José M Jiménez-Gómez
Circadian period and phase of cultivated tomato ( Solanum lycopersicum ) were changed during domestication, likely adapting the species to its new agricultural environments. Whereas the delayed circadian phase is mainly caused by allelic variation of EID1 , the genetic basis of the long circadian period has remained elusive. Here we show that a partial deletion of the clock gene LNK2 is responsible for the period lengthening in cultivated tomatoes. We use resequencing data to phylogenetically classify hundreds of tomato accessions and investigate the evolution of the eid1 and lnk2 mutations along successive domestication steps...
May 22, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29788236/a-novel-adeno-associated-virus-capsid-with-enhanced-neurotropism-corrects-a-lysosomal-transmembrane-enzyme-deficiency
#6
Julie Tordo, Claire O'Leary, André S L M Antunes, Nuria Palomar, Patrick Aldrin-Kirk, Mark Basche, Antonette Bennett, Zelpha D'Souza, Hélène Gleitz, Annie Godwin, Rebecca J Holley, Helen Parker, Ai Yin Liao, Paul Rouse, Amir Saam Youshani, Larbi Dridi, Carla Martins, Thierry Levade, Kevin B Stacey, Daniel M Davis, Adam Dyer, Nathalie Clément, Tomas Björklund, Robin R Ali, Mavis Agbandje-McKenna, Ahad A Rahim, Alexey Pshezhetsky, Simon N Waddington, R Michael Linden, Brian W Bigger, Els Henckaerts
Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties...
May 16, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29788219/exploiting-metamerism-to-regulate-the-impact-of-a-visual-display-on-alertness-and-melatonin-suppression-independent-of-visual-appearance
#7
Annette E Allen, Esther M Hazelhoff, Franck P Martial, Christian Cajochen, Robert J Lucas
Objectives: Artificial light sources such as visual display units (VDUs) elicit a range of subconscious and reflex light responses, including increases in alertness and suppression of pineal melatonin. Such responses employ dedicated retinal circuits encompassing melanopsin photoreceptors. Here, we aimed to determine whether this arrangement can be exploited to modulate the impact of VDUs on melatonin onset and alertness without altering visual appearance. Methods: We generated a 5-primary VDU capable of presenting metameric movies (matched for colour and luminance) but varying in melanopic-irradiance...
May 18, 2018: Sleep
https://www.readbyqxmd.com/read/29788202/quantitative-proteomics-reveals-neuronal-ubiquitination-of-rngo-ddi1-and-several-proteasomal-subunits-by-ube3a-accounting-for-the-complexity-of-angelman-syndrome
#8
Juanma Ramirez, Benoit Lectez, Nerea Osinalde, Monika Sivá, Nagore Elu, Kerman Aloria, Michaela Procházková, Coralia Perez, Jose Martínez-Hernández, Rosa Barrio, Klára Grantz Šašková, Jesus M Arizmendi, Ugo Mayor
Angelman syndrome is a complex neurodevelopmental disorder caused by the lack of function in the brain of a single gene, UBE3A. The E3 ligase coded by this gene is known to build K48-linked ubiquitin chains, a modification historically considered to target substrates for degradation by the proteasome. However, a change in protein abundance is not proof that a candidate UBE3A substrate is indeed ubiquitinated by UBE3A. We have here used an unbiased ubiquitin proteomics approach, the bioUb strategy, to identify 79 proteins that appear more ubiquitinated in the Drosophila photoreceptor cells when Ube3a is over-expressed...
June 1, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29785047/rationally-designed-aav2-and-aavrh8r-capsids-provide-improved-transduction-in-the-retina-and-brain
#9
Jennifer A Sullivan, Lisa M Stanek, Michael J Lukason, Jie Bu, Shayla R Osmond, Elizabeth A Barry, Catherine R O'Riordan, Lamya S Shihabuddin, Seng H Cheng, Abraham Scaria
The successful application of adeno-associated virus (AAV) gene delivery vectors as a therapeutic paradigm will require efficient gene delivery to the appropriate cells in affected organs. In this study, we utilized a rational design approach to introduce modifications to the AAV2 and AAVrh8R capsids and the resulting variants were evaluated for transduction activity in the retina and brain. The modifications disrupted either capsid/receptor binding or altered capsid surface charge. Specifically, we mutated AAV2 amino acids R585A and R588A, which are required for binding to its receptor, heparan sulfate proteoglycans, to generate a variant referred to as AAV2-HBKO...
May 22, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29784939/automatic-cone-photoreceptor-localisation-in-healthy-and-stargardt-afflicted-retinas-using-deep-learning
#10
Benjamin Davidson, Angelos Kalitzeos, Joseph Carroll, Alfredo Dubra, Sebastien Ourselin, Michel Michaelides, Christos Bergeles
We present a robust deep learning framework for the automatic localisation of cone photoreceptor cells in Adaptive Optics Scanning Light Ophthalmoscope (AOSLO) split-detection images. Monitoring cone photoreceptors with AOSLO imaging grants an excellent view into retinal structure and health, provides new perspectives into well known pathologies, and allows clinicians to monitor the effectiveness of experimental treatments. The MultiDimensional Recurrent Neural Network (MDRNN) approach developed in this paper is the first method capable of reliably and automatically identifying cones in both healthy retinas and retinas afflicted with Stargardt disease...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29783078/delayed-bipolar-and-ganglion-cells-neuroretinal-processing-in-regular-cannabis-users-the-retina-as-a-relevant-site-to-investigate-brain-synaptic-transmission-dysfunctions
#11
Thomas Schwitzer, Raymund Schwan, Karine Angioi-Duprez, Anne Giersch, Laurence Lalanne, Eliane Albuisson, Vincent Laprevote
Cannabis use is widespread worldwide, but the impact of smoking cannabis regularly on brain synaptic transmission has only been partially elucidated. The retina is considered as an easy means of determining dysfunction in brain synaptic transmission. The endocannabinoid system is involved in regulating retinal synaptic transmission, which might also be affected by tobacco. Previous preliminary results have shown impairments in retinal ganglion cell response in cannabis users. Here, we test the extent to which earlier retinal levels-bipolar cells and photoreceptors-are affected in cannabis users, i...
May 1, 2018: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/29782826/sheets-of-human-retinal-progenitor-transplants-improve-vision-in-rats-with-severe-retinal-degeneration
#12
Bin Lin, Bryce T McLelland, Anuradha Mathur, Robert B Aramant, Magdalene J Seiler
Loss of photoreceptors and other retinal cells is a common endpoint in retinal degenerate (RD) diseases that cause blindness. Retinal transplantation is a potential therapy to replace damaged retinal cells and improve vision. In this study, we examined the development of human fetal retinal sheets with or without their retinal pigment epithelium (RPE) transplanted to immunodeficient retinal degenerate rho S334ter-3 rats. Sheets were dissected from fetal human eyes (11-15.7 weeks gestation) and then transplanted to the subretinal space of 24-31 d old RD nude rats...
May 18, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29781741/slowly-progressive-retinitis-pigmentosa-caused-by-two-novel-mutations-in-the-mak-gene
#13
Joanna Monika Gray, Harry Otway Orlans, Morag Shanks, Penny Clouston, Robert Elvis MacLaren
BACKGROUND: The growing number of clinical trials currently underway for inherited retinal diseases has highlighted the importance of achieving a molecular diagnosis for all new cases presenting to hospital eye services. The male germ cell-associated kinase (MAK) gene encodes a cilium-associated protein selectively expressed in the retina and testis, and has recently been implicated in autosomal recessive retinitis pigmentosa (RP). Whole exome sequencing has previously identified a homozygous Alu insertion in probands with recessive RP and nonsense and missense mutations have also been reported...
May 21, 2018: Ophthalmic Genetics
https://www.readbyqxmd.com/read/29781190/in-situ-study-of-the-functions-of-bacterioruberin-in-the-dual-chromophore-photoreceptor-archaerhodopsin-4
#14
Chao Sun, Xiaoyan Ding, Haolin Cui, Yanan Yang, Sijin Chen, Anthony Watts, Xin Zhao
While certain archaeal ion pumps have been shown to contain two chromophores, retinal and carotenoid bacterioruberin, the functions of the bacterioruberin have not been well explored. To address this research gap, the recombinant archaerhodopsin-4 (aR4), either with retinal chromophore only or with both retinal and bacterioruberin chromophores, was successfully expressed together with endogenous lipids in H. salinarum L33 and MPK409 respectively. In situ solid-state NMR, supported by molecular spectroscopy and functional assays, revealed for the first time that the retinal thermal equilibrium in the dark-adapted state is modulated by bacterioruberin binding via a cluster of aromatic residues on helix E...
May 20, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29780953/micropulse-laser-for-persistent-optic-disc-pit-maculopathy-a-case-report
#15
Carlos Andrés Valdés-Lara, Nicolás Crim, Gerardo García-Aguirre, Ismael Ávila Lule, Virgilio Morales-Cantón
Purpose: Optic disc pits (ODP) are rare and congenital anomalies of the optic disc, sometimes remaining asymptomatic. However, serous macular detachment or optic disc maculopathy is the most common complication, causing significant visual deterioration, without a current consensus about treatment. We describe a case of ODP maculopathy that was treated successfully with micropulse laser. Observations: A patient with ODP maculopathy remained with macular serous detachment after nine months of follow up after pars plana vitrectomy...
June 2018: American Journal of Ophthalmology Case Reports
https://www.readbyqxmd.com/read/29780913/cryptococcal-choroiditis-in-advanced-aids-with-clinicopathologic-correlation
#16
Christopher M Aderman, Ian R Gorovoy, Daniel L Chao, Michele M Bloomer, Anthony Obeid, Jay M Stewart
Purpose: To describe a case of disseminated cryptococcal meningitis with multifocal choroiditis and provide optical coherence tomography (OCT) findings correlated with described histopathology in a patient with advanced acquired immunodeficiency syndrome (AIDS). Observations: The patient was a 54-year-old man with AIDS who presented with dyspnea and headache followed by acute vision loss. OCT demonstrated a lesion with a small area of fluid that was limited by a more prominent and irregular external limiting membrane with underlying nodular choroidal thickening, mild RPE disorganization, and hyperreflectivity of the overlying photoreceptor layer...
June 2018: American Journal of Ophthalmology Case Reports
https://www.readbyqxmd.com/read/29779871/non-canonical-phototransduction-mediates-synchronization-of-the-drosophila-melanogaster-circadian-clock-and-retinal-light-responses
#17
Maite Ogueta, Roger C Hardie, Ralf Stanewsky
The daily light-dark cycles represent a key signal for synchronizing circadian clocks. Both insects and mammals possess dedicated "circadian" photoreceptors but also utilize the visual system for clock resetting. In Drosophila, circadian clock resetting is achieved by the blue-light photoreceptor cryptochrome (CRY), which is expressed within subsets of the brain clock neurons. In addition, rhodopsin-expressing photoreceptor cells contribute to light synchronization. Light resets the molecular clock by CRY-dependent degradation of the clock protein Timeless (TIM), although in specific subsets of key circadian pacemaker neurons, including the small ventral lateral neurons (s-LNvs), TIM and Period (PER) oscillations can be synchronized by light independent of CRY and canonical visual Rhodopsin phototransduction...
April 30, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29778783/intra-vitreal-%C3%AE-b-crystallin-fused-to-elastin-like-polypeptide-provides-neuroprotection-in-a-mouse-model-of-age-related-macular-degeneration
#18
Parameswaran G Sreekumar, Zhe Li, Wan Wang, Christine Spee, David R Hinton, Ram Kannan, J Andrew MacKay
Age-related macular degeneration (AMD) is the leading cause of severe and irreversible central vision loss, and the primary site of AMD pathology is the retinal pigment epithelium (RPE). Geographic atrophy (GA) is an advanced form of AMD characterized by extensive RPE cell loss, subsequent degeneration of photoreceptors, and thinning of retina. This report describes the protective potential of a peptide derived from the αB crystallin protein using a sodium iodate (NaIO3 ) induced mouse model of GA. Systemic NaIO3 challenge causes degeneration of the RPE and neighboring photoreceptors, which have similarities to retinas of GA patients...
May 17, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29777959/extracellular-matrix-expression-in-human-pluripotent-stem-cell-derived-retinal-organoids-recapitulates-retinogenesis-in-vivo-and-reveals-an-important-role-for-impg1-and-cd44-in-the-development-of-photoreceptors-and-interphotoreceptor-matrix
#19
Majed Felemban, Birthe Dorgau, Nicola Claire Hunt, Dean Hallam, Darin Zerti, Roman Bauer, Yuchun Ding, Joseph Collin, David Steel, Natalio Krasnogor, Jumana Al-Aama, Susan Lindsay, Carla Mellough, Majlinda Lako
The extracellular matrix (ECM) plays an important role in numerous processes including cellular proliferation, differentiation, migration, maturation, adhesion guidance and axonal growth. To date, there has been no detailed analysis of the ECM distribution during retinal ontogenesis in humans and the functional importance of many ECM components is poorly understood. In this study, the expression of key ECM components in adult mouse and monkey retina, developing and adult human retina and retinal organoids derived from human pluripotent stem cells was studied...
May 16, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29777677/usherin-defects-lead-to-early-onset-retinal-dysfunction-in-zebrafish
#20
Margo Dona, Ralph Slijkerman, Kimberly Lerner, Sanne Broekman, Jeremy Wegner, Taylor Howat, Theo Peters, Lisette Hetterschijt, Nando Boon, Erik de Vrieze, Nasrin Sorusch, Uwe Wolfrum, Hannie Kremer, Stephan Neuhauss, Jingjing Zang, Maarten Kamermans, Monte Westerfield, Jennifer Phillips, Erwin van Wijk
Mutations in USH2A are the most frequent cause of Usher syndrome and autosomal recessive nonsyndromic retinitis pigmentosa. To unravel the pathogenic mechanisms underlying USH2A-associated retinal degeneration and to evaluate future therapeutic strategies that could potentially halt the progression of this devastating disorder, an animal model is needed. The available Ush2a knock-out mouse model does not mimic the human phenotype, because it presents with only a mild and late-onset retinal degeneration. Using CRISPR/Cas9-technology, we introduced protein-truncating germline lesions into the zebrafish ush2a gene (ush2armc1 : c...
May 16, 2018: Experimental Eye Research
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