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https://www.readbyqxmd.com/read/29785047/rationally-designed-aav2-and-aavrh8r-capsids-provide-improved-transduction-in-the-retina-and-brain
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/29775763/photoreceptor-mediated-regulation-of-the-cop1-spa-e3-ubiquitin-ligase
#13
REVIEW
Roman Podolec, Roman Ulm
Plants have evolved specific photoreceptors that capture informational cues from sunlight. The phytochrome, cryptochrome, and UVR8 photoreceptors perceive red/far-red, blue/UV-A, and UV-B light, respectively, and control overlapping photomorphogenic responses important for plant growth and development. A major repressor of such photomorphogenic responses is the E3 ubiquitin ligase formed by CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) and SUPPRESSOR OF PHYA-105 (SPA) proteins, which acts by regulating the stability of photomorphogenesis-promoting transcription factors...
May 15, 2018: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/29775563/anolis-carolinensis-as-a-model-to-understand-molecular-and-cellular-basis-of-foveal-development
#14
Naif S Sannan, Xianghong Shan, Kevin Gregory-Evans, Kenro Kusumi, Cheryl Y Gregory-Evans
The fovea is an anatomical specialization of the central retina containing closely packed cone-photoreceptors providing an area of high acuity vision in humans and primates. Despite its key role in the clarity of vision, little is known about the molecular and cellular basis of foveal development, due to the absence of a foveal structure in commonly used laboratory animal models. Of the amniotes the retina in birds of prey and some reptiles do exhibit a typical foveal structure, but they have not been studied in the context of foveal development due to lack of availability of embryonic tissue, lack of captive breeding programs, and limited genomic information...
May 15, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29775503/artificial-rod-and-cone-photoreceptors-with-human-like-spectral-sensitivities
#15
Byeongho Park, Heehong Yang, Tai Hwan Ha, Hyun Seo Park, Seung Ja Oh, Yong-Sang Ryu, Youngho Cho, Hyo-Suk Kim, Juyeong Oh, Dong Kyu Lee, Chulki Kim, Taikjin Lee, Minah Seo, Jaebin Choi, Young Min Jhon, Deok Ha Woo, Seok Lee, Seok Hwan Kim, Hyuk-Jae Lee, Seong Chan Jun, Hyun Seok Song, Tai Hyun Park, Jae Hun Kim
Photosensitive materials contain biologically engineered elements and are constructed using delicate techniques, with special attention devoted to efficiency, stability, and biocompatibility. However, to date, no photosensitive material has been developed to replace damaged visual-systems to detect light and transmit the signal to a neuron in the human body. In the current study, artificial nanovesicle-based photosensitive materials are observed to possess the characteristics of photoreceptors similar to the human eye...
May 18, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29774302/ocular-histopathology-and-immunohistochemical-analysis-in-the-oldest-known-individual-with-autosomal-dominant-vitreoretinochoroidopathy
#16
Morton F Goldberg, Scott McLeod, Mark Tso, Kirk Packo, Malia Edwards, Imran A Bhutto, Rajkumar Baldeosingh, Charles Eberhart, Bernhard H F Weber, Gerard A Lutty
Purpose: To assess the immunohistochemical and histopathological changes in a subject with Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC). Design: Case study. Participant: Ninety two year-old Caucasian male with ADVIRC. Methods: The subject was documented clinically for 54 Years. The retina/choroid complex of the right eye was evaluated with cryosections stained with hematoxylin and eosin or periodic acid schiff reagent...
April 2018: Ophthalmology Retina
https://www.readbyqxmd.com/read/29773814/melanopsin-mediated-pupil-function-is-impaired-in-parkinson-s-disease
#17
Daniel S Joyce, Beatrix Feigl, Graham Kerr, Luisa Roeder, Andrew J Zele
Parkinson's disease (PD) is characterised by non-motor symptoms including sleep and circadian disruption. Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGC) transmit light signals to brain areas controlling circadian rhythms and the pupil light reflex. To determine if non-motor symptoms observed in PD are linked to ipRGC dysfunction, we evaluated melanopsin and rod/cone contributions to the pupil response in medicated participants with PD (n = 17) and controls (n = 12)...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773803/a-novel-small-molecule-chaperone-of-rod-opsin-and-its-potential-therapy-for-retinal-degeneration
#18
Yuanyuan Chen, Yu Chen, Beata Jastrzebska, Marcin Golczak, Sahil Gulati, Hong Tang, William Seibel, Xiaoyu Li, Hui Jin, Yong Han, Songqi Gao, Jianye Zhang, Xujie Liu, Hossein Heidari-Torkabadi, Phoebe L Stewart, William E Harte, Gregory P Tochtrop, Krzysztof Palczewski
Rhodopsin homeostasis is tightly coupled to rod photoreceptor cell survival and vision. Mutations resulting in the misfolding of rhodopsin can lead to autosomal dominant retinitis pigmentosa (adRP), a progressive retinal degeneration that currently is untreatable. Using a cell-based high-throughput screen (HTS) to identify small molecules that can stabilize the P23H-opsin mutant, which causes most cases of adRP, we identified a novel pharmacological chaperone of rod photoreceptor opsin, YC-001. As a non-retinoid molecule, YC-001 demonstrates micromolar potency and efficacy greater than 9-cis-retinal with lower cytotoxicity...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29771303/visual-impairment-and-progressive-phthisis-bulbi-caused-by-recessive-pathogenic-variant-in-mark3
#19
Muhammad Ansar, Hyunglok Chung, Yar M Waryah, Periklis Makrythanasis, Emilie Falconnet, Ali Raza Rao, Michel Guipponi, Ashok K Narsani, Ralph Fingerhut, Federico A Santoni, Emmanuelle Ranza, Ali M Waryah, Hugo J Bellen, Stylianos E Antonarakis
Developmental eye defects often severely reduce vision. Despite extensive efforts, for a substantial fraction of these cases the molecular causes are unknown. Recessive eye disorders are frequent in consanguineous populations and such large families with multiple affected individuals provide an opportunity to identify recessive causative genes. We studied a Pakistani consanguineous family with three affected individuals with congenital vision loss and progressive eye degeneration. The family was analyzed by exome sequencing of one affected individual and genotyping of all family members...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29770905/congenital-grouped-albinotic-spots-of-the-retinal-pigment-epithelium-in-a-patient-with-hemihypertrophy-and-caf%C3%A3-au-lait-spots
#20
Eugenia C White, Jesse D Sengillo, Galaxy Y Cho, Mathieu F Bakhoum, Stephen H Tsang
PURPOSE: To describe the finding of circularly grouped hypomelanotic spots in the central macula of a patient with syndromic characteristics. METHODS: Case report of a patient with albinotic spots grouped within the macula, café au lait spots, and left-sided hemihypertrophy. RESULTS: A 15-year-old boy presented with hypomelanotic spots which were hyperautofluorescent on fundus autofluorescence imaging with no disruption of the retinal laminae or photoreceptor inner and outer segment (IS/OS) junction on spectral domain optical coherence tomography...
May 16, 2018: Documenta Ophthalmologica. Advances in Ophthalmology
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