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https://www.readbyqxmd.com/read/28734946/impaired-rhodopsin-generation-in-the-rat-model-of-diabetic-retinopathy
#1
Volha V Malechka, Gennadiy Moiseyev, Yusuke Takahashi, Younghwa Shin, Jian-Xing Ma
Diabetic retinopathy is a common complication of diabetes mellitus. Diabetic patients experience functional deficits in dark adaptation, contrast sensitivity, and color perception before microvascular pathologies become apparent. Here, we evaluated early changes in neural retinal function and in retinoid metabolism in the eye in diabetes. Streptozotocin-induced diabetic rats showed decreased a-wave and b-wave amplitudes of scotopic and photopic electroretinography responses four months after diabetes induction compared to nondiabetic controls...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28731695/how-rhodopsin-tunes-the-equilibrium-between-protonated-and-deprotonated-forms-of-the-retinal-chromophore
#2
Siri Camee van Keulen, Alicia Solano, Ursula Rothlisberger
Rhodopsin is a photoactive G-protein-coupled receptor (GPCR) that converts dim light into a signal for the brain, leading to eyesight. Full activation of this GPCR is achieved after passing through several steps of the protein's photoactivation pathway. Key events of rhodopsin activation are the initial cis-trans photoisomerisation of the covalently bound retinal moiety followed by conformational rearrangements and deprotonation of the chromophore's protonated Schiff base (PSB), which ultimately lead to full activation in the meta II state...
July 21, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28730104/down-regulation-of-protein-kinase-c-alpha-ezrin-signals-in-light-induced-phagocytic-crisis-of-retinal-pigment-epithelium-cells
#3
Ya-Qiong Zhang, Yong-Gang Fan, Ya-Long Dang, Yan-Li Liu, Hua Liu, Li-Hua Li
AIM: To investigate the roles of PKC-α/ezrin signals in phagocytosis crisis of retinal pigment epithelium (RPE) cells in light damage model. METHODS: Light induced mice RPE injury model was established by continuously irradiating cool white light at different exposure time (0, 4, 8h light intensity: 4.18×10(-6) J/cm(2)). In vitro, human ARPE-19 cells treated with the doses and intensity (1.57×10(-6) J/cm(2)) of laser irradiation. Histology analysis was evaluated by hematoxylin and eosin (HE) staining...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28729419/the-exocyst-is-required-for-photoreceptor-ciliogenesis-and-retinal-development
#4
Glenn P Lobo, Diana Fulmer, Lilong Guo, Xiaofeng Zuo, Yujing Dang, Seok-Hyung Kim, Yanhui Su, Kola George, Elisabeth Obert, Ben Fogelgren, Deepak Nihalani, Russell A Norris, Bärbel Rohrer, Joshua H Lipschutz
We previously have shown that the highly-conserved eight-protein exocyst trafficking complex is required for ciliogenesis in kidney tubule cells. We hypothesized here that ciliogenic programs are conserved across organs and species. To determine if renal primary ciliogenic programs are conserved in the eye, and to characterize the function and mechanisms by which the exocyst regulates eye development in zebrafish, we focused on exoc5, a central component of the exocyst complex, by analyzing both exoc5 zebrafish mutants, and photoreceptor-specific Exoc5 knockout mice...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28728913/considerations-in-repetitive-activation-of-light-sensitive-ion-channels-for-long-term-studies-channel-rhodopsin-in-the-drosophila-model
#5
Jake Higgins, Christina Hermanns, Cole Malloy, Robin L Cooper
Optogenetics is a technique used in various animal models and holds a potential for therapeutic possibilities in mammals. There are technical issues with the use of light sensitive ion channels: reproducible effects over time, controlling where the non-native proteins are targeted within the cell and changes in the biophysical properties of the cells they are expressed in. We used a variant of channel rhodopsin (ChR2-XXL) and targeted expression in neurons of larval Drosophila to investigate the acute and chronic activation, with light pulses, of the channels on synaptic function...
July 17, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28728517/using-molecular-dynamics-for-the-refinement-of-atomistic-models-of-gpcrs-by-homology-modeling
#6
Cecylia S Lupala, Bahareh Rasaeifar, Patricia Gomez-Gutierrez, Juan J Perez
Despite GPCRs share a common seven helix bundle, analysis of the diverse crystallographic structures available reveal specific features that might be relevant for ligand design. Despite the number of crystallographic structures of GPCRs is steadily increasing, there are still challenges that hamper the availability of new structures. In the absence of a crystallographic structure, homology modelling remains one of the important techniques for constructing 3D models of proteins. In the present study we investigated the use of molecular dynamics simulations for the refinement of GPCRs models constructed by homology modeling...
July 20, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28728472/the-identification-of-interferon-%C3%AE-as-a-key-supportive-factor-for-retinal-differentiation-of-murine-mesenchymal-stem-cells
#7
Barbora Hermankova, Jan Kossl, Eliska Javorkova, Pavla Bohacova, Michaela Hajkova, Alena Zajicova, Magdalena Krulova, Vladimir Holan
Retinal disorders represent the main cause of decreased quality of vision and even blindness worldwide. The loss of retinal cells causes irreversible damage of the retina and there are currently no effective treatment protocols for most retinal degenerative diseases. A promising approach for the treatment of retinal disorders is represented by stem cell-based therapy. The perspective candidates are mesenchymal stem cells (MSCs) which can differentiate into multiple cell types and produce a number of trophic and growth factors...
July 20, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28728042/pharmacological-relationships-and-ligand-discovery-of-g-protein-coupled-receptors-revealed-by-simultaneous-ligand-and-receptor-clustering
#8
Cheng Zhang, Yi-Ming Shao, Xiaohua Ma, Siew Lee Cheong, Chu Qin, Lin Tao, Peng Zhang, Shangying Chen, Xian Zeng, Hongxia Liu, Giorgia Pastorin, Yuyang Jiang, Yu Zong Chen
Conventional ligand and receptor similarity methods have been extensively used for exposing pharmacological relationships and drug lead discovery. They may in some cases neglect minor relationships useful for target hopping particularly against the remote family members. To complement the conventional methods for capturing these minor relationships, we developed a new method that uses a SLARC (Simultaneous Ligand And Receptor Clustering) 2D map to simultaneously characterize the ligand structural and receptor binding-site sequence relationships of a receptor family...
July 11, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28720880/pattern-of-retinal-morphological-and-functional-decay-in-a-light-inducible-rhodopsin-mutant-mouse
#9
Claudia Gargini, Elena Novelli, Ilaria Piano, Martina Biagioni, Enrica Strettoi
Hallmarks of Retinitis Pigmentosa (RP), a family of genetic diseases, are a typical rod-cone-degeneration with initial night blindness and loss of peripheral vision, followed by decreased daylight sight and progressive visual acuity loss up to legal blindness. Great heterogeneity in nature and function of mutated genes, variety of mutations for each of them, variability in phenotypic appearance and transmission modality contribute to make RP a still incurable disease. Translational research relies on appropriate animal models mimicking the genetic and phenotypic diversity of the human pathology...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715844/effects-of-pathogenic-variations-in-the-human-rhodopsin-gene-hrho-on-the-predicted-accessibility-for-a-lead-candidate-ribozyme
#10
Beau R Froebel, Alexandria J Trujillo, Jack M Sullivan
Purpose: The mutation-independent strategy for hammerhead ribozyme (hhRz) or RNA interference (RNAi)-based gene therapeutics to treat autosomal dominant diseases is predicated on the hypothesis that a single therapeutic would equivalently suppress all/most of the diverse mutant mRNAs in patients with the disease phenotype. However, the hypothesis has not been formally tested. We address this through a comprehensive bioinformatics study of how mutations affect target mRNA structure accessibility for a single lead hhRz therapeutic (725GUC↓), designed against human rod rhodopsin mRNA (hRHO), for patients with hRHO mutations that cause autosomal dominant retinitis pigmentosa...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28705596/isolation-and-characterization-of-aerobic-anoxygenic-phototrophs-from-exposed-soils-from-the-s%C3%A3-r-rondane-mountains-east-antarctica
#11
Guillaume Tahon, Anne Willems
This study investigated the culturable aerobic phototrophic bacteria present in soil samples collected in the proximity of the Belgian Princess Elisabeth Station in the Sør Rondane Mountains, East Antarctica. Until recently, only oxygenic phototrophic bacteria (Cyanobacteria) were well known from Antarctic soils. However, more recent non-cultivation-based studies have demonstrated the presence of anoxygenic phototrophs and, particularly, aerobic anoxygenic phototrophic bacteria in these areas. Approximately 1000 isolates obtained after prolonged incubation under different growth conditions were studied and characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry...
June 27, 2017: Systematic and Applied Microbiology
https://www.readbyqxmd.com/read/28700926/the-energetics-of-chromophore-binding-in-the-visual-photoreceptor-rhodopsin
#12
He Tian, Thomas P Sakmar, Thomas Huber
The visual photoreceptor rhodopsin is a prototypical G-protein-coupled receptor (GPCR) that stabilizes its inverse agonist ligand, 11-cis-retinal (11CR), by a covalent, protonated Schiff base linkage. In the visual dark adaptation, the fundamental molecular event after photobleaching of rhodopsin is the recombination reaction between its apoprotein opsin and 11CR. Here we present a detailed analysis of the kinetics and thermodynamics of this reaction, also known as the "regeneration reaction". We compared the regeneration of purified rhodopsin reconstituted into phospholipid/detergent bicelles with rhodopsin reconstituted into detergent micelles...
July 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28700348/mechanisms-of-phosphenes-in-irradiated-patients
#13
REVIEW
Thibaud Mathis, Stephane Vignot, Cecila Leal, Jean-Pierre Caujolle, Celia Maschi, Martine Mauget-Faÿsse, Laurent Kodjikian, Stéphanie Baillif, Joel Herault, Juliette Thariat
Anomalous visual perceptions have been reported in various diseases of the retina and visual pathways or can be experienced under specific conditions in healthy individuals. Phosphenes are perceptions of light in the absence of ambient light, occurring independently of the physiological and classical photonic stimulation of the retina. They are a frequent symptom in patients irradiated in the region of the central nervous system (CNS), head and neck and the eyes. Phosphenes have historically been attributed to complex physical phenomena such as Cherenkov radiation...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28691584/fibrin-gel-as-a-scaffold-for-photoreceptor-cells-differentiation-from-conjunctiva-mesenchymal-stem-cells-in-retina-tissue-engineering
#14
Mostafa Soleimannejad, Somayeh Ebrahimi-Barough, Masoud Soleimani, Samad Nadri, Seyed Mohammad Tavangar, Ramak Roohipoor, Meysam Yazdankhah, Neda Bayat, Mohammad Riazi-Esfahani, Jafar Ai
Stem cell-based therapies are attraction approaches for regenerative medicine for treating retinal diseases. One of the limitations in cell therapy is cell death following post-injection whit preventing functional integration with retinal tissue. Fibrin gel, a bio-polymeric material with excellent biocompatibility, provides numerous advantages as a tissue engineering scaffold and a stem cell carrier. Therefore, current research is focusing on developing fibrin hydrogel scaffolds to protect stem cells during delivery and to stimulate endogenous regeneration through interactions of transplanted stem cells and retinal tissue...
July 10, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28689420/reply-to-comment-on-transient-conformational-changes-of-sensory-rhodopsin-ii-investigated-by-vibrational-stark-effect-probes
#15
Hendrik Mohrmann, Joachim Heberle
No abstract text is available yet for this article.
July 24, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28689400/comment-on-transient-conformational-changes-of-sensory-rhodopsin-ii-investigated-by-vibrational-stark-effect-probes
#16
Steven G Boxer
No abstract text is available yet for this article.
July 24, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28678424/the-metabolic-syndrome-alters-the-mirna-signature-of-porcine-adipose-tissue-derived-mesenchymal-stem-cells
#17
Yu Meng, Alfonso Eirin, Xiang-Yang Zhu, Hui Tang, Pritha Chanana, Amir Lerman, Andre J Van Wijnen, Lilach O Lerman
Autologous transplantation of mesenchymal stem cells (MSCs) is a viable option for the treatment of several diseases. Evidence indicates that MSCs release extracellular vesicles (EVs) and that EVs shuttle miRNAs to damaged parenchymal cells to activate an endogenous repair program. We hypothesize that comorbidities may interfere with the packaging of cargo in MSC-derived EVs. Therefore, we examined whether metabolic syndrome (MetS) modulates the miRNA content packed within MSC-derived EVs. MSCs were collected from swine abdominal adipose tissue after 16 weeks of lean or obese diet (n = 7 each)...
July 5, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28676737/gene-therapy-in-a-large-animal-model-of-pde6a-retinitis-pigmentosa
#18
Freya M Mowat, Laurence M Occelli, Joshua T Bartoe, Kristen J Gervais, Ashlee R Bruewer, Janice Querubin, Astra Dinculescu, Sanford L Boye, William W Hauswirth, Simon M Petersen-Jones
Despite mutations in the rod phosphodiesterase 6-alpha (PDE6A) gene being well-recognized as a cause of human retinitis pigmentosa, no definitive treatments have been developed to treat this blinding disease. We performed a trial of retinal gene augmentation in the Pde6a mutant dog using Pde6a delivery by capsid-mutant adeno-associated virus serotype 8, previously shown to have a rapid onset of transgene expression in the canine retina. Subretinal injections were performed in 10 dogs at 29-44 days of age, and electroretinography and vision testing were performed to assess functional outcome...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28672005/fatty-acid-transport-protein-1-regulates-retinoid-metabolism-and-photoreceptor-development-in-mouse-retina
#19
Aurélie Cubizolle, Laurent Guillou, Bertrand Mollereau, Christian P Hamel, Philippe Brabet
In retinal pigment epithelium (RPE), RPE65 catalyzes the isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol in the visual cycle and controls the rhodopsin regeneration rate. However, the mechanisms by which these processes are regulated are still unclear. Fatty Acid Transport Protein 1 (FATP1) is involved in fatty acid uptake and lipid metabolism in a variety of cell types. FATP1 co-localizes with RPE65 in RPE and inhibits its isomerase activity in vitro. Here, we further investigated the role of FATP1 in the visual cycle using transgenic mice that overexpress human FATP1 specifically in the RPE (hFATP1TG mice)...
2017: PloS One
https://www.readbyqxmd.com/read/28657745/recent-advances-in-structure-based-drug-design-targeting-class-a-g-protein-coupled-receptors-utilizing-crystal-structures-and-computational-simulations
#20
Yoonji Lee, Shaherin Basith, Sun Choi
G protein-coupled receptors (GPCRs) represent the largest and most physiologically important integral membrane protein family, and these receptors respond to a wide variety of physiological and environmental stimuli. GPCRs are among the most critical therapeutic targets for numerous human diseases, and approximately one-third of the currently marketed drugs target this receptor family. The recent breakthroughs in GPCR structural biology have significantly contributed to our understanding of GPCR function, ligand binding, and pharmacological action as well as to the design of new drugs...
July 21, 2017: Journal of Medicinal Chemistry
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