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https://www.readbyqxmd.com/read/27918826/long-term-protection-of-genetically-ablated-rabbit-retinal-degeneration-by-sustained-transscleral-unoprostone-delivery
#1
Nobuhiro Nagai, Eri Koyanagi, Yasuko Izumida, Junjun Liu, Aya Katsuyama, Hirokazu Kaji, Matsuhiko Nishizawa, Noriko Osumi, Mineo Kondo, Hiroko Terasaki, Yukihiko Mashima, Toru Nakazawa, Toshiaki Abe
Purpose: To evaluate the long-term protective effects of transscleral unoprostone (UNO) against retinal degeneration in transgenic (Tg) rabbits (Pro347Leu rhodopsin mutation). Methods: The UNO release devices (URDs) were implanted into the sclerae of Tg rabbits and ERG, optical coherence tomography (OCT), and ophthalmic examinations were conducted for 40 weeks. Unoprostone metabolites in retina, choroid/RPE, aqueous humor, and plasma from wild-type (Wt) rabbits were measured using liquid chromatography-tandem mass spectrometry...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27901172/conformational-states-of-hamp-domains-interacting-with-sensory-rhodopsin-membrane-systems-an-integrated-all-atom-and-coarse-grained-molecular-dynamics-simulation-approach
#2
Bikash Ranjan Sahoo, Toshimichi Fujiwara
Understanding the downstream signaling mechanism of sensory rhodopsin and its cognate transducer complex (srII-htrII) has long been a challenge in the field of photoreceptor research. Here, an integration of all-atom and coarse-grained (CG) molecular dynamics (MD) simulations in different srII-htrII complex states is carried out. It is shown that the cytoplasmic four-helix HAMP dimer gives rise to a gear-box model interaction with discrete hydrophobic packing in Natronomonas pharaonis (Np). Structural analysis in all-atom and CG-MD reveals a stable conformational state in the physiological environment (323 K and 1...
November 30, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27893855/inhibition-of-matrix-metalloproteinase-9-enhances-rod-survival-in-the-s334ter-line3-retinitis-pigmentosa-model
#3
Jung-A Shin, Hwa Sun Kim, Andrew Vargas, Wan-Qing Yu, Yun Sung Eom, Cheryl Mae Craft, Eun-Jin Lee
Retinitis Pigmentosa (RP) is one of the most common forms of inherited visual loss with the initial degeneration of rod photoreceptors, followed by a progressive cone photoreceptor deterioration. Coinciding with this visual loss, the extracellular matrix (ECM) is reorganized, which alters matrix metalloproteinase (MMP) activity levels. A potential pathological role of MMPs, MMP-9 in particular, involves an excitotoxicity-mediated physiological response. In the current study, we examine the MMP-9 and MMP-2 expression levels in the rhodopsin S334ter-line3 RP rat model and investigate the impact of treatment with SB-3CT, a specific MMP-9 and MMP-2 inhibitor, on rod cell survival was tested...
2016: PloS One
https://www.readbyqxmd.com/read/27893831/retinal-pre-conditioning-by-cd59a-knockout-protects-against-light-induced-photoreceptor-degeneration
#4
Delu Song, Brooks Wilson, Liangliang Zhao, Rupak Bhuyan, Mausumi Bandyopadhyay, Arkady Lyubarsky, Chen Yu, Yafeng Li, Levi Kanu, Takashi Miwa, Wen-Chao Song, Silvia C Finnemann, Bärbel Rohrer, Joshua L Dunaief
Complement dysregulation plays a key role in the pathogenesis of age-related macular degeneration (AMD), but the specific mechanisms are incompletely understood. Complement also potentiates retinal degeneration in the murine light damage model. To test the retinal function of CD59a, a complement inhibitor, CD59a knockout (KO) mice were used for light damage (LD) experiments. Retinal degeneration and function were compared in WT versus KO mice following light damage. Gene expression changes, endoplasmic reticulum (ER) stress, and glial cell activation were also compared...
2016: PloS One
https://www.readbyqxmd.com/read/27883057/the-warburg-effect-mediator-pyruvate-kinase-m2-expression-and-regulation-in-the-retina
#5
Raju V S Rajala, Ammaji Rajala, Christopher Kooker, Yuhong Wang, Robert E Anderson
The tumor form of pyruvate kinase M2 (PKM2) undergoes tyrosine phosphorylation and gives rise to the Warburg effect. The Warburg effect defines a pro-oncogenic metabolism switch such that cancer cells take up more glucose than normal tissue and favor incomplete oxidation of glucose, even in the presence of oxygen. Retinal photoreceptors are highly metabolic and their energy consumption is equivalent to that of a multiplying tumor cell. In the present study, we found that PKM2 is the predominant isoform in both rod- and cone-dominant retina, and that it undergoes a light-dependent tyrosine phosphorylation...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881908/functional-study-of-two-biochemically-unusual-mutations-in-gucy2d-leber-congenital-amaurosis-expressed-via-adenoassociated-virus-vector-in-mouse-retinas
#6
Sanford L Boye, Elena V Olshevskaya, Igor V Peshenko, K Tyler McCullough, Shannon E Boye, Alexander M Dizhoor
PURPOSE: To test, in living photoreceptors, two mutations, S248W and R1091x, in the GUCY2D gene linked to Leber congenital amaurosis 1 (LCA1) that fail to inactivate the catalytic activity of a heterologously expressed retinal membrane guanylyl cyclase 1 (RetGC1). METHODS: GUC2YD cDNA constructs coding for wild-type human (hWT), R1091x, and S248W GUCY2D under the control of the human rhodopsin kinase promoter were expressed in Gucy2e(-/-)Gucy2f(-/-) knockout (GCdKO) mouse retinas, which lack endogenous RetGC activity...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27874856/in-vivo-editing-of-the-human-mutant-rhodopsin-gene-by-electroporation-of-plasmid-based-crispr-cas9-in-the-mouse-retina
#7
Maria Carmela Latella, Maria Teresa Di Salvo, Fabienne Cocchiarella, Daniela Benati, Giulia Grisendi, Antonella Comitato, Valeria Marigo, Alessandra Recchia
The bacterial CRISPR/Cas system has proven to be an efficient tool for genetic manipulation in various organisms. Here we show the application of CRISPR-Cas9 technology to edit the human Rhodopsin (RHO) gene in a mouse model for autosomal dominant Retinitis Pigmentosa. We designed single or double sgRNAs to knock-down mutant RHO expression by targeting exon 1 of the RHO gene carrying the P23H dominant mutation. By delivering Cas9 and sgRNAs in a single plasmid we induced an efficient gene editing in vitro, in HeLa cells engineered to constitutively express the P23H mutant RHO allele...
November 22, 2016: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/27865136/ph-dependent-absorption-spectra-of-rhodopsin-mutant-e113q-on-the-role-of-counterions-and-protein
#8
Peng Xie, Panwang Zhou, Ahmed Alsaedi, Yan Zhang
The absorption spectra of bovine rhodopsin mutant E113Q in solutions were investigated at the molecular level by using a hybrid quantum mechanics/molecular mechanics (QM/MM) method. The calculations suggest the mechanism of the absorption variations of E113Q at different pH values. The results indicate that the polarizations of the counterions in the vicinity of Schiff base under protonation and unprotonation states of the mutant E113Q would be a crucial factor to change the energy gap of the retinal to tune the absorption spectra...
November 13, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/27862951/characterization-and-evolution-of-the-spotted-gar-retina
#9
Joshua M Sukeena, Carlos A Galicia, Jacob D Wilson, Tim McGinn, Janette W Boughman, Barrie D Robison, John H Postlethwait, Ingo Braasch, Deborah L Stenkamp, Peter G Fuerst
In this study, we characterize the retina of the spotted gar, Lepisosteus oculatus, a ray-finned fish. Gar did not undergo the whole genome duplication event that occurred at the base of the teleost fish lineage, which includes the model species zebrafish and medaka. The divergence of gars from the teleost lineage and the availability of a high-quality genome sequence make it a uniquely useful species to understand how genome duplication sculpted features of the teleost visual system, including photoreceptor diversity...
November 9, 2016: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/27861619/a-chimera-na-pump-rhodopsin-as-an-effective-optogenetic-silencer
#10
Mohammad Razuanul Hoque, Toru Ishizuka, Keiichi Inoue, Rei Abe-Yoshizumi, Hiroyuki Igarashi, Takaaki Mishima, Hideki Kandori, Hiromu Yawo
With the progress of optogenetics, the activities of genetically identified neurons can be optically silenced to determine whether the neurons in question are necessary for the network performance of the behavioral expression. This logical induction is expected to be improved by the application of the Na+ pump rhodopsins (NaRs), which hyperpolarize the membrane potential with negligible influence on the ionic/pH balance. Here, we made several chimeric NaRs between two NaRs, KR2 and IaNaR from Krokinobacter eikastus and Indibacter alkaliphilus, respectively...
2016: PloS One
https://www.readbyqxmd.com/read/27859420/the-light-driven-sodium-ion-pump-a-new-player-in-rhodopsin-research
#11
Hideaki E Kato, Keiichi Inoue, Hideki Kandori, Osamu Nureki
Rhodopsins are one of the most studied photoreceptor protein families, and ion-translocating rhodopsins, both pumps and channels, have recently attracted broad attention because of the development of optogenetics. Recently, a new functional class of ion-pumping rhodopsins, an outward Na(+) pump, was discovered, and following structural and functional studies enable us to compare three functionally different ion-pumping rhodopsins: outward proton pump, inward Cl(-) pump, and outward Na(+) pump. Here, we review the current knowledge on structure-function relationships in these three light-driven pumps, mainly focusing on Na(+) pumps...
November 17, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27856246/reprogramming-of-retinoblastoma-cancer-cells-into-cancer-stem-cells
#12
Fengming Yue, Kanji Hirashima, Daihachiro Tomotsune, Sakiko Takizawa-Shirasawa, Tadayuki Yokoyama, Katsunori Sasaki
Retinoblastoma is the most common intraocular malignancy in pediatric patients. It develops rapidly in the retina and can be fatal if not treated promptly. It has been proposed that a small population of cancer cells, termed cancer stem cells (CSCs), initiate tumorigenesis from immature tissue stem cells or progenitor cells. Reprogramming technology, which can convert mature cells into pluripotent stem cells (iPS), provides the possibility of transducing malignant cancer cells back to CSCs, a type of early stage of cancer...
November 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27853152/a-natural-light-driven-inward-proton-pump
#13
Keiichi Inoue, Shota Ito, Yoshitaka Kato, Yurika Nomura, Mikihiro Shibata, Takayuki Uchihashi, Satoshi P Tsunoda, Hideki Kandori
Light-driven outward H(+) pumps are widely distributed in nature, converting sunlight energy into proton motive force. Here we report the characterization of an oppositely directed H(+) pump with a similar architecture to outward pumps. A deep-ocean marine bacterium, Parvularcula oceani, contains three rhodopsins, one of which functions as a light-driven inward H(+) pump when expressed in Escherichia coli and mouse neural cells. Detailed mechanistic analyses of the purified proteins reveal that small differences in the interactions established at the active centre determine the direction of primary H(+) transfer...
November 17, 2016: Nature Communications
https://www.readbyqxmd.com/read/27849063/vibrational-resonance-allostery-and-activation-in-rhodopsin-like-g-protein-coupled-receptors
#14
Kristina N Woods, Jürgen Pfeffer, Arpana Dutta, Judith Klein-Seetharaman
G protein-coupled receptors are a large family of membrane proteins activated by a variety of structurally diverse ligands making them highly adaptable signaling molecules. Despite recent advances in the structural biology of this protein family, the mechanism by which ligands induce allosteric changes in protein structure and dynamics for its signaling function remains a mystery. Here, we propose the use of terahertz spectroscopy combined with molecular dynamics simulation and protein evolutionary network modeling to address the mechanism of activation by directly probing the concerted fluctuations of retinal ligand and transmembrane helices in rhodopsin...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27848911/phospholipase-d-activity-couples-plasma-membrane-endocytosis-with-retromer-dependent-recycling
#15
Rajan Thakur, Aniruddha Panda, Elise Coessens, Nikita Raj, Shweta Yadav, Sruthi Balakrishnan, Qifeng Zhang, Plamen Georgiev, Bishal Basak, Renu Pasricha, Michael Jo Wakelam, Nicholas T Ktistakis, Padinjat Raghu
During illumination, the light-sensitive plasma membrane (rhabdomere) of Drosophila photoreceptors undergoes turnover with consequent changes in size and composition. However, the mechanism by which illumination is coupled to rhabdomere turnover remains unclear. We find that photoreceptors contain a light-dependent phospholipase D (PLD) activity. During illumination, loss of PLD resulted in an enhanced reduction in rhabdomere size, accumulation of Rab7 positive, rhodopsin1-containing vesicles (RLVs) in the cell body and reduced rhodopsin protein...
November 16, 2016: ELife
https://www.readbyqxmd.com/read/27836700/coupled-hoop-signature-correlates-with-quantum-yield-of-isorhodopsin-and-analog-pigments
#16
Petra H M Bovee-Geurts, Johan Lugtenburg, Willem J DeGrip
With a quantum yield of 0.66±0.03 the photoisomerization efficiency of the visual pigment rhodopsin (11-cis⇒all-trans chromophore) is exceptionally high. This is currently explained by coherent coupling of the excited state electronic wavepacket with local vibrational nuclear modes, facilitating efficient cross-over at a conical intersection onto the photoproduct energy surface. The 9-cis counterpart of rhodopsin, dubbed isorhodopsin, has a much lower quantum yield (0.26±0.03), which, however, can be markedly enhanced by modification of the retinal chromophore (7,8-dihydro and 9-cyclopropyl derivatives)...
November 9, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27830666/theoretical-description-of-protein-field-effects-on-electronic-excitations-of-biological-chromophores
#17
Daniele Varsano, Stefano Caprasecca, Emanuele Coccia
Photoinitiated phenomena play a crucial role in many living organisms. Plants, algae, and bacteria absorb sunlight to perform photosynthesis, and convert water and carbon dioxide into molecular oxygen and carbohydrates, thus forming the basis for life on Earth. The vision of vertebrates is accomplished in the eye by a protein called rhodopsin, which upon photon absorption performs an ultrafast isomerisation of the retinal chromophore, triggering the signal cascade. Many other biological functions start with the photoexcitation of a protein-embedded pigment, followed by complex processes comprising, for example, electron or excitation energy transfer in photosynthetic complexes...
November 10, 2016: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/27820927/south-american-weakly-electric-fish-gymnotiformes-are-long-wavelength-sensitive-cone-monochromats
#18
Da-Wei Liu, Ying Lu, Hong Young Yan, Harold H Zakon
Losses of cone opsin genes are noted in animals that are nocturnal or rely on senses other than vision. We investigated the cone opsin repertoire of night-active South American weakly electric fish. We obtained opsin gene sequences from genomic DNA of 3 gymnotiforms (Eigenmannia virescens, Sternopygus macrurus, Apteronotus albifrons) and the assembled genome of the electric eel (Electrophorus electricus). We identified genes for long-wavelength-sensitive (LWS) and medium-wavelength-sensitive cone opsins (RH2) and rod opsins (RH1)...
November 8, 2016: Brain, Behavior and Evolution
https://www.readbyqxmd.com/read/27818291/c-terminal-motif-of-human-neuropeptide-y4-receptor-determines-internalization-and-arrestin-recruitment
#19
Lizzy Wanka, Stefanie Babilon, Kerstin Burkert, Karin Mörl, Vsevolod V Gurevich, Annette G Beck-Sickinger
The human neuropeptide Y4 receptor is a rhodopsin-like G protein-coupled receptor (GPCR), which contributes to anorexigenic signals. Thus, this receptor is a highly interesting target for metabolic diseases. As GPCR internalization and trafficking affect receptor signaling and vice versa, we aimed to investigate the molecular mechanism of hY4R desensitization and endocytosis. The role of distinct segments of the hY4R carboxyl terminus was investigated by fluorescence microscopy, binding assays, inositol turnover experiments and bioluminescence resonance energy transfer assays to examine the internalization behavior of hY4R and its interaction with arrestin-3...
November 3, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27815287/microbial-and-viral-like-rhodopsins-present-in-coastal-marine-sediments-from-four-polar-and-subpolar-regions
#20
J L López, M Golemba, E Hernández, M Lozada, H M Dionisi, J Jansson, J Carroll, L Lundgren, S Sjöling, W P Mac Cormack
Rhodopsins are broadly distributed. In this work we analyzed 23 metagenomes corresponding to marine sediment samples from four regions which share cold climate conditions (Norway; Sweden; Argentina and Antarctica). In order to investigate the genes evolution of viral-rodopsins, an initial set of 6224 bacterial rhodopsins sequences according COG5524 were retrieved from the 23 metagenomes. After selection by the presence of transmembrane domains and alignment 123 viral (51) and non-viral (72) sequences (>50 aminoacids) were finally included in further analysis...
November 3, 2016: FEMS Microbiology Ecology
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