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https://www.readbyqxmd.com/read/27933535/systems-genetics-analysis-to-identify-the-genetic-modulation-of-a-glaucoma-associated-gene
#1
Sumana R Chintalapudi, Monica M Jablonski
Loss of retinal ganglion cells (RGCs) is one of the hallmarks of retinal neurodegenerative diseases, glaucoma being one of the most common. Recently, γ-synuclein (SNCG) was shown to be highly expressed in the somas and axons of RGCs. In various mouse models of glaucoma, downregulation of Sncg gene expression correlates with RGC loss. To investigate the regulation of Sncg in RGCs, we used a systems genetics approach to identify a gene that modulates the expression of Sncg, followed by confirmatory studies in both healthy and diseased retinas...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933534/genomic-control-of-retinal-cell-number-challenges-protocol-and-results
#2
Patrick W Keeley, Irene E Whitney, Benjamin E Reese
This chapter considers some of the challenges in obtaining accurate and consistent estimates of neuronal population size in the mouse retina, in order to identify the genetic control of cell number through QTL mapping and candidate gene analysis. We first discuss a variety of best practices for analyzing large numbers of recombinant inbred strains of mice over the course of a year in order to amass a satisfactory dataset for QTL mapping. We then consider the relative merits of using average cell density versus estimated total cell number as the target trait to be assessed, and why estimates of heritability may differ for these two traits when studying the retina in whole-mount preparations...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27933306/significant-changes-in-endogenous-retinal-gene-expression-assessed-1-year-after-a-single-intraocular-injection-of-aav-cntf-or-aav-bdnf
#3
Chrisna J LeVaillant, Anil Sharma, Jill Muhling, Lachlan Pg Wheeler, Greg S Cozens, Mats Hellström, Jennifer Rodger, Alan R Harvey
Use of viral vectors to deliver therapeutic genes to the central nervous system holds promise for the treatment of neurodegenerative diseases and neurotrauma. Adeno-associated viral (AAV) vectors encoding brain-derived neurotrophic factor (BDNF) or ciliary derived neurotrophic factor (CNTF) promote the viability and regeneration of injured adult rat retinal ganglion cells. However, these growth-inducing transgenes are driven by a constitutively active promoter, thus we examined whether long-term AAV-mediated secretion of BDNF or CNTF affected endogenous retinal gene expression...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933220/a-novel-method-for-quantitative-serial-autofluorescence-analysis-in-retinitis-pigmentosa-using-image-characteristics
#4
Jasleen K Jolly, Siegfried K Wagner, Jonathan Moules, Florian Gekeler, Andrew R Webster, Susan M Downes, Robert E MacLaren
PURPOSE: Identifying potential biomarkers for disease progression in retinitis pigmentosa (RP) is highly relevant now that gene therapy and other treatments are in clinical trial. Here we report a novel technique for analysis of short-wavelength autofluorescence (AF) imaging to quantify defined regions of AF in RP patients. METHODS: Fifty-five-degree AF images were acquired from 12 participants with RP over a 12-month period. Of these, five were identified as having a hyperfluorescent annulus...
December 2016: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/27933051/short-interfering-rna-inhibits-rift-valley-fever-virus-replication-and-degradation-of-protein-kinase-r-in-human-cells
#5
Bonto Faburay, Juergen A Richt
Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing severe outbreaks in humans and livestock in sub-Saharan Africa and the Arabian Peninsula. Human infections are characterized by fever, sometimes leading to encephalitis, retinitis, hemorrhagic fever, and occasionally death. There are currently no fully licensed vaccines or effective therapies for human use. Gene silencing mediated by double-stranded short interfering RNA (siRNA) is a sequence-specific, highly conserved mechanism in eukaryotes, which serves as an antiviral defense mechanism...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27932954/neuronal-release-of-cytokine-il-3-triggered-by-mechanosensitive-autostimulation-of-the-p2x7-receptor-is-neuroprotective
#6
Jason C Lim, Wennan Lu, Jonathan M Beckel, Claire H Mitchell
Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead to both pro-inflammatory and neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes. While cytokine signaling in neural systems is often associated with glial cells like astrocytes and microglia, the contribution of neurons themselves to the cytokine response is underappreciated and has bearing on any balanced response...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27932951/high-pressure-induced-mtdna-alterations-in-retinal-ganglion-cells-and-subsequent-apoptosis
#7
Sheng-Hai Zhang, Feng-Juan Gao, Zhong-Mou Sun, Ping Xu, Jun-Yi Chen, Xing-Huai Sun, Ji-Hong Wu
Purpose: Our previous study indicated that mitochondrial DNA (mtDNA) damage and mutations are crucial to the progressive loss of retinal ganglion cells (RGCs) in a glaucomatous rat model. In this study, we examined whether high pressure could directly cause mtDNA alterations and whether the latter could lead to mitochondrial dysfunction and RGC death. Methods: Primary cultured rat RGCs were exposed to 30 mm Hg of hydrostatic pressure (HP) for 12, 24, 48, 72, 96 and 120 h. mtDNA alterations and mtDNA repair/replication enzymes OGG1, MYH and polymerase gamma (POLG) expressions were also analyzed...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27932942/loss-of-fractalkine-signaling-exacerbates-axon-transport-dysfunction-in-a-chronic-model-of-glaucoma
#8
Kevin T Breen, Sarah R Anderson, Michael R Steele, David J Calkins, Alejandra Bosco, Monica L Vetter
Neurodegeneration in glaucoma results in decline and loss of retinal ganglion cells (RGCs), and is associated with activation of myeloid cells such as microglia and macrophages. The chemokine fractalkine (FKN or Cx3cl1) mediates communication from neurons to myeloid cells. Signaling through its receptor Cx3cr1 has been implicated in multiple neurodegenerative diseases, but the effects on neuronal pathology are variable. Since it is unknown how FKN-mediated crosstalk influences RGC degeneration in glaucoma, we assessed this in a chronic mouse model, DBA/2J...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27932898/two-cases-of-vogt-koyanagi-harada-s-disease-in-sub-saharan-africa
#9
Tunji S Oluleye, Adekunle O Rotimi-Samuel, Adetunji Adenekan, Olubanke T Ilo, Folashade B Akinsola, Adeola O Onakoya, Olufisayo T Aribaba, Adebukunola Adefule-Ositelu, Kareem O Musa, Yele Oyefeso
Vogt-Koyanagi-Harada's (VKH) disease has been reported to be rare in sub-Saharan Africa. Two Nigerians with the disease are presented in this report. The first patient, a 32-year-old pregnant Nigerian woman presented with a 1-month history of bilateral blurring of vision, persistent headache, and alopecia. Presenting visual acuity was 1 m counting fingers in both eyes. Examination revealed vitiligo and poliosis with bilateral panuveitis as well as bilateral exudative retinal detachment. A clinical assessment of complete VKH disease was made...
2016: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/27932857/vogt-koyanagi-harada-syndrome-current-perspectives
#10
REVIEW
Abeir Baltmr, Sue Lightman, Oren Tomkins-Netzer
Vogt-Koyanagi-Harada syndrome is a cause of noninfectious panuveitis, leading to significant vision loss in many patients. It is an autoimmune disease occurring in genetically susceptible individuals and clinically presents as bilateral panuveitis with serous retinal detachments and hyperemic, swollen optic discs, which are associated with neurological and auditory manifestations. Early diagnosis and prompt and adequate treatment with immunosuppressive agents (corticosteroids and other immunosuppressive drugs) may halt disease progression and prevent recurrences and vision loss...
2016: Clinical Ophthalmology
https://www.readbyqxmd.com/read/27932223/relationship-between-psychophysical-measures-of-retinal-ganglion-cell-density%C3%A2-and-in%C3%A2-vivo-measures-of-cone-density%C3%A2-in-glaucoma
#11
Juliane Matlach, Pádraig J Mulholland, Marketa Cilkova, Reena Chopra, Nilpa Shah, Tony Redmond, Steven C Dakin, David F Garway-Heath, Roger S Anderson
PURPOSE: Considerable between-individual variation in retinal ganglion cell (RGC) density exists in healthy individuals, making identification of change from normal to glaucoma difficult. In ascertaining local cone-to-RGC density ratios in healthy individuals, we wished to investigate the usefulness of objective cone density estimates as a surrogate of baseline RGC density in glaucoma patients, and thus a more efficient way of identifying early changes. DESIGN: Exploratory cohort study...
December 5, 2016: Ophthalmology
https://www.readbyqxmd.com/read/27931222/mir-15a-16-reduces-retinal-leukostasis-through-decreased-pro-inflammatory-signaling
#12
Eun-Ah Ye, Li Liu, Youde Jiang, Jenny Jan, Subhash Gaddipati, Susmit Suvas, Jena J Steinle
BACKGROUND: Hyperglycemia is a significant risk factor for diabetic retinopathy and induces increased inflammatory responses and retinal leukostasis, as well as vascular damage. Although there is an increasing amount of evidence that miRNA may be involved in the regulation in the pathology of diabetic retinopathy, the mechanisms by which miRNA mediate cellular responses to control onset and progression of diabetic retinopathy are still unclear. The purpose of our study was to investigate the hypothesis that miR-15a/16 inhibit pro-inflammatory signaling to reduce retinal leukostasis...
December 8, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27930977/eupatilin-prevents-h2o2-induced-oxidative-stress-and-apoptosis-in-human-retinal-pigment-epithelial-cells
#13
Lei Du, Jia Chen, Yi-Qiao Xing
Eupatilin, a pharmacologically active flavone derived from the Artemisia plant species, is known to possess anti-oxidant activity. However, the effects of eupatilin on oxidative stress-induced retinal damage in retinal pigment epithelium (RPE) cells and the potential mechanisms involved have not been explored. Therefore, the aim of this study was to investigate the effects of eupatilin on oxidative stress-induced retinal damage in RPE cells. Our results showed that eupatilin significantly attenuated H2O2-induced cell injury and ROS production in ARPE-19 cells...
December 5, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27930778/melanopsin-containing-or-non-melanopsin-containing-retinal-ganglion-cells-response-to-acute-ocular-hypertension-with-or-without-brain-derived-neurotrophic-factor-neuroprotection
#14
Giuseppe Rovere, Francisco M Nadal-Nicolás, Jiawei Wang, Jose M Bernal-Garro, Nuria García-Carrillo, Maria Paz Villegas-Pérez, Marta Agudo-Barriuso, Manuel Vidal-Sanz
Purpose: To analyze the responses of different retinal ganglion cell (RGC) types to acute ocular hypertension (AOH) and intravitreal administration of brain-derived neurotrophic factor (BDNF). Methods: In adult albino rats, the anterior chamber of the left eye was cannulated with a needle connected to a saline container elevated 1½ meters above the eye for 75 minutes. Rats received 12 hours before a 5 μl intravitreal injection containing 5 μg BDNF in 1% albumin PBS or vehicle and were analyzed 3, 7, 14, or 45 days later...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27930757/association-between-regular-cannabis-use-and-ganglion-cell-dysfunction
#15
Thomas Schwitzer, Raymund Schwan, Eliane Albuisson, Anne Giersch, Laurence Lalanne, Karine Angioi-Duprez, Vincent Laprevote
Importance: Because cannabis use is a major public health concern and cannabis is known to act on central neurotransmission, studying the retinal ganglion cells in individuals who regularly use cannabis is of interest. Objective: To determine whether the regular use of cannabis could alter the function of retinal ganglion cells in humans. Design, Setting, and Participants: For this case-control study, individuals who regularly use cannabis, as well as healthy controls, were recruited, and data were collected from February 11 to October 28, 2014...
December 8, 2016: JAMA Ophthalmology
https://www.readbyqxmd.com/read/27930756/a-revised-approach-for-the-detection-of-sight-threatening-diabetic-macular-edema
#16
Taras V Litvin, George H Bresnick, Jorge A Cuadros, Steve Selvin, Kuniyoshi Kanai, Glen Y Ozawa
Importance: Diabetic macular edema is one of the leading causes of vision loss among working-age adults in the United States. Telemedicine screening programs and epidemiological studies rely on monoscopic fundus photography for the detection of clinically significant macular edema (CSME). Improving the accuracy of detecting CSME from monoscopic images could be valuable while recognizing the limitations of such detection in an era of optical coherence tomography detection of diabetic macular edema...
December 8, 2016: JAMA Ophthalmology
https://www.readbyqxmd.com/read/27930731/serum-autoantibody-profiling-of-patients-with-paraneoplastic-and-non-paraneoplastic-autoimmune-retinopathy
#17
Josianne C Ten Berge, Joost van Rosmalen, Jacolien Vermeer, Cecilia Hellström, Cecilia Lindskog, Peter Nilsson, Ulrika Qundos, Aniki Rothova, Marco W J Schreurs
PURPOSE: Although multiple serum antiretinal autoantibodies (ARAs) have been reported in patients with paraneoplastic and non-paraneoplastic autoimmune retinopathy ((n)pAIR), not all retinal antigens involved in (n)pAIR are specified. This study aims to serologically identify patients with presumed (n)pAIR through determination of both known and unknown ARAs by autoantibody profiling. METHODS: An antigen suspension bead array using 188 different antigens representing 97 ocular proteins was performed to detect ARAs in serum samples of patients with presumed (n)pAIR (n = 24), uveitis (n = 151) and cataract (n = 21)...
2016: PloS One
https://www.readbyqxmd.com/read/27930693/endothelin-b-receptors-on-primary-chicken-m%C3%A3-ller-cells-and-the-human-mio-m1-m%C3%A3-ller-cell-line-activate-erk-signaling-via-transactivation-of-epidermal-growth-factor-receptors
#18
Mohammad Harun-Or-Rashid, Dardan Konjusha, Caridad Galindo-Romero, Finn Hallböök
Injury to the eye or retina triggers Müller cells, the major glia cell of the retina, to dedifferentiate and proliferate. In some species they attain retinal progenitor properties and have the capacity to generate new neurons. The epidermal growth factor receptor (EGFR) system and extracellular signal-regulated kinase (ERK) signaling are key regulators of these processes in Müller cells. The extracellular signals that modulate and control these processes are not fully understood. In this work we studied whether endothelin receptor signaling can activate EGFR and ERK signaling in Müller cells...
2016: PloS One
https://www.readbyqxmd.com/read/27930654/whole-organism-developmental-expression-profiling-identifies-rab-28-as-a-novel-ciliary-gtpase-associated-with-the-bbsome-and-intraflagellar-transport
#19
Victor L Jensen, Stephen Carter, Anna A W M Sanders, Chunmei Li, Julie Kennedy, Tiffany A Timbers, Jerry Cai, Noemie Scheidel, Breandán N Kennedy, Ryan D Morin, Michel R Leroux, Oliver E Blacque
Primary cilia are specialised sensory and developmental signalling devices extending from the surface of most eukaryotic cells. Defects in these organelles cause inherited human disorders (ciliopathies) such as retinitis pigmentosa and Bardet-Biedl syndrome (BBS), frequently affecting many physiological and developmental processes across multiple organs. Cilium formation, maintenance and function depend on intracellular transport systems such as intraflagellar transport (IFT), which is driven by kinesin-2 and IFT-dynein motors and regulated by the Bardet-Biedl syndrome (BBS) cargo-adaptor protein complex, or BBSome...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27930646/retinal-expression-of-the-drosophila-eyes-absent-gene-is-controlled-by-several-cooperatively-acting-cis-regulatory-elements
#20
Bonnie M Weasner, Brandon P Weasner, Sarah D Neuman, Arash Bashirullah, Justin P Kumar
The eyes absent (eya) gene of the fruit fly, Drosophila melanogaster, is a member of an evolutionarily conserved gene regulatory network that controls eye formation in all seeing animals. The loss of eya leads to the complete elimination of the compound eye while forced expression of eya in non-retinal tissues is sufficient to induce ectopic eye formation. Within the developing retina eya is expressed in a dynamic pattern and is involved in tissue specification/determination, cell proliferation, apoptosis, and cell fate choice...
December 2016: PLoS Genetics
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