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Retinal regeneration

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https://www.readbyqxmd.com/read/29133431/restoration-of-dendritic-complexity-functional-connectivity-and-diversity-of-regenerated-retinal-bipolar-neurons-in-adult-zebrafish
#1
Timothy E McGinn, Diana M Mitchell, Peter C Meighan, Natalie Partington, Dylan C Leoni, Christina E Jenkins, Michael D Varnum, Deborah L Stenkamp
Adult zebrafish (Danio rerio) are capable of regenerating retinal neurons that have been lost due to mechanical, chemical, or light damage. In the case of chemical damage, there is evidence that visually-mediated behaviors are restored following regeneration, consistent with recovery of retinal function. However, the extent to which regenerated retinal neurons attain appropriate morphologies and circuitry after such tissue-disrupting lesions has not been investigated. Adult zebrafish of both sexes were subjected to intravitreal injections of ouabain, which destroys the inner retina...
November 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29113466/perspectives-of-stem-cell-based-therapy-for-age-related-retinal-degenerative-diseases
#2
Vladimir Holan, Barbora Hermankova, Jan Kossl
Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and glaucoma, mostly affect the elderly population and are the most common cause of decreased quality of vision or even blindness. So far, there is no satisfactory treatment protocol to prevent, stop, or cure these disorders. A great hope and promise for patients suffering from retinal diseases is represented by stem cell-based therapy that could replace diseased or missing retinal cells and support regeneration...
September 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29109681/tenascins-in-retinal-and-optic-nerve-neurodegeneration
#3
REVIEW
Jacqueline Reinhard, Lars Roll, Andreas Faissner
Tenascins represent key constituents of the extracellular matrix (ECM) with major impact on central nervous system (CNS) development. In this regard, several studies indicate that they play a crucial role in axonal growth and guidance, synaptogenesis and boundary formation. These functions are not only important during development, but also for regeneration under several pathological conditions. Additionally, tenascin-C (Tnc) represents a key modulator of the immune system and inflammatory processes. In the present review article, we focus on the function of Tnc and tenascin-R (Tnr) in the diseased CNS, specifically after retinal and optic nerve damage and degeneration...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29098663/antibiotics-reduce-retinal-cell-survival-in-vitro
#4
Amy E Lindsey, Ellen Townes-Anderson
Antibiotics such as gentamicin (an aminoglycoside) and penicillin (a beta-lactam antibiotic) are routinely used in retinal cell and explant cultures. In many cases, these in vitro systems are testing parameters regarding photoreceptor transplantation or preparing cells for transplantation. In vivo, milligram doses of gentamicin are neurotoxic to the retina. However, little is known about the effects of antibiotics to retina in vitro and whether smaller doses of gentamicin are toxic to retinal cells. To test toxicity, retinal cells were dissociated from tiger salamander, placed in culture, and treated with either 20 μg/ml gentamicin, 100 μg/ml streptomycin, 100 U/ml antibiotic/antimycotic, 0...
November 2, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29079576/ablation-of-the-riboflavin-binding-protein-retbindin-reduces-flavin-levels-and-leads-to-progressive-and-dose-dependent-degeneration-of-rods-and-cones
#5
Ryan A Kelley, Muayyad R Al-Ubaidi, Tirthankar Sinha, Ayse M Genc, Mustafa S Makia, Larissa Ikelle, Muna I Naash
The interface between the neural retina and the retinal pigment epithelium (RPE) is critical for several processes, including visual pigment regeneration and retinal attachment to the RPE. One of its most important functions is the exchange of metabolites between the photoreceptors and RPE because photoreceptor cells have very high energy demands, largely satisfied by oxidative metabolism. The riboflavin (RF) cofactors, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) are two key cofactors involved in oxidative metabolism...
October 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29078372/dephosphorylation-by-protein-phosphatase-2a-regulates-visual-pigment-regeneration-and-the-dark-adaptation-of-mammalian-photoreceptors
#6
Alexander V Kolesnikov, Tivadar Orban, Hui Jin, Celine Brooks, Lukas Hofmann, Zhiqian Dong, Maxim Sokolov, Krzysztof Palczewski, Vladimir J Kefalov
Resetting of G-protein-coupled receptors (GPCRs) from their active state back to their biologically inert ground state is an integral part of GPCR signaling. This "on-off" GPCR cycle is regulated by reversible phosphorylation. Retinal rod and cone photoreceptors arguably represent the best-understood example of such GPCR signaling. Their visual pigments (opsins) are activated by light, transduce the signal, and are then inactivated by a GPCR kinase and arrestin. Although pigment inactivation by phosphorylation is well understood, the enzyme(s) responsible for pigment dephosphorylation and the functional significance of this reaction remain unknown...
October 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29062223/enhancing-the-efficacy-of-areds-antioxidants-in-light-induced-retinal-degeneration
#7
Paul Wong, M Markey, C M Rapp, R M Darrow, A Ziesel, D T Organisciak
PURPOSE: Light-induced photoreceptor cell degeneration and disease progression in age-related macular degeneration (AMD) involve oxidative stress and visual cell loss, which can be prevented, or slowed, by antioxidants. Our goal was to test the protective efficacy of a traditional Age-related Eye Disease Study antioxidant formulation (AREDS) and AREDS combined with non-traditional antioxidants in a preclinical animal model of photooxidative retinal damage. METHODS: Male Sprague-Dawley rats were reared in a low-intensity (20 lux) or high-intensity (200 lux) cyclic light environment for 6 weeks...
2017: Molecular Vision
https://www.readbyqxmd.com/read/29048427/hdac6-inhibition-by-tubastatin-a-is-protective-against-oxidative-stress-in-a-photoreceptor-cell-line-and-restores-visual-function-in-a-zebrafish-model-of-inherited-blindness
#8
Janina Leyk, Conor Daly, Ulrike Janssen-Bienhold, Breandán N Kennedy, Christiane Richter-Landsberg
Retinal diseases, such as hereditary retinitis pigmentosa and age-related macular degeneration, are characterized by the progressive loss of photoreceptors. Histone deacetylase 6 (HDAC6) is considered as a stress surveillance factor and a potential target for neuroprotection and regeneration. Overexpression of HDAC6 has been connected to neurodegenerative disorders, and its suppression may provide protection. Here we show that HDAC6 is constitutively present in the mouse retina, and in the cone-like mouse cell line 661W...
August 31, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29030175/characterization-of-the-pleiotropic-roles-of-sonic-hedgehog-during-retinal-regeneration-in-adult-zebrafish
#9
Jennifer L Thomas, Gregory W Morgan, Kaylee M Dolinski, Ryan Thummel
In contrast to the mammalian retina, the zebrafish retina possesses the ability to regenerate. This is primarily accomplished through Müller glial cells, which, upon damage, re-enter the cell cycle to form retinal progenitors. The progenitors continue to proliferate as they migrate to the area of damage and ultimately differentiate into new neurons. The purpose of this study was to characterize the expression and function of Sonic Hedgehog (Shh) during regeneration of the adult zebrafish retina. Expression profiling of Shh pathway genes showed a significant upregulation of expression associated with stages of progenitor proliferation and neuronal differentiation...
October 10, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28989053/pdgfs-and-their-receptors-in-vascular-stem-progenitor-cells-functions-and-therapeutic-potential-in-retinal-vasculopathy
#10
REVIEW
Weisi Lu, Xuri Li
Vascular stem/progenitor cells (VSCs) include endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and mesenchymal stem cells. VSCs can produce functional and mature vascular cells required to build blood vessels. VSCs therefore play critical roles in vascular repair and regeneration, particularly, in various retinal vasculopathies, in which vascular defects are a devastating pathology. The platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are important regulators of numerous physiological events and diseases, and they play key roles in regulating the formation and function of blood vessels...
October 6, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28983586/directed-transdifferentiation-of-m%C3%A3-ller-glial-cells-to-photoreceptors-using-the-sonic-hedgehog-signaling-pathway-agonist-purmorphamine
#11
Dandan Gu, Songtao Wang, Shuai Zhang, Peng Zhang, Guomin Zhou
Specification of distinct cell types from Müller glial cells is key to the potential application of endogenous repair in retinal regeneration. Sonic hedgehog (SHH) has been established as a potent mitogen for rat Müller glial cells, which also induces Müller glial cells to dedifferentiate and adopt the phenotype of rod photoreceptors. The present study investigated the effects of purmorphamine, a small molecule that activates the SHH‑pathway, in the proliferation, dedifferentiation and transdifferentiation of Müller glial cells, as determined by several methods including immunofluorescence, polymerase chain reaction and western blotting...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28966629/live-cell-imaging-new-avenues-to-investigate-retinal-regeneration
#12
REVIEW
Manuela Lahne, David R Hyde
Sensing and responding to our environment requires functional neurons that act in concert. Neuronal cell loss resulting from degenerative diseases cannot be replaced in humans, causing a functional impairment to integrate and/or respond to sensory cues. In contrast, zebrafish (Danio rerio) possess an endogenous capacity to regenerate lost neurons. Here, we will focus on the processes that lead to neuronal regeneration in the zebrafish retina. Dying retinal neurons release a damage signal, tumor necrosis factor α, which induces the resident radial glia, the Müller glia, to reprogram and re-enter the cell cycle...
August 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28951213/a-novel-function-of-neuroglobin-for-neuroregeneration-in-mice-after-optic-nerve-injury
#13
Kayo Sugitani, Yoshiki Koriyama, Mayuko Sera, Kunizo Arai, Kazuhiro Ogai, Keisuke Wakasugi
Neuroglobin (Ngb) is a recently discovered heme protein in the vertebrate brain that can bind to oxygen molecules. Mammalian Ngb plays a crucial role in neuroprotection under conditions of oxidative stress. To investigate other potential functions of Ngb, we investigated the mouse retinal Ngb system following optic nerve injury. In the retina of control mice, Ngb immunoreactivity was limited to the retinal ganglion cell (RGC) layer, and this immunoreactivity rapidly decreased to less than 50% of the control level 5 days after optic nerve injury...
November 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28936466/mouse-m%C3%A3-ller-cell-isolation-and-culture
#14
Xiao Liu, Luosheng Tang, Yongqing Liu
Müller cells are the major supportive and protective glial cells across the retina. Unlike in fish, they have lost the capacity to regenerate the retina in mammals. But, mammalian Müller cells still retain certain retinal stem cell properties with various degree of self-renewal and differentiation potentials, and thereby held a merit in cell-based therapies for treating retinal degeneration diseases. In our laboratory, we use an enzymatic procedure to isolate, purify, and culture mouse Müller cells.
August 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28935984/regulation-of-axonal-regeneration-by-the-level-of-function-of-the-endogenous-nogo-receptor-antagonist-lotus
#15
Tomoko Hirokawa, Yixiao Zou, Yuji Kurihara, Zhaoxin Jiang, Yusuke Sakakibara, Hiromu Ito, Kengo Funakoshi, Nobutaka Kawahara, Yoshio Goshima, Stephen M Strittmatter, Kohtaro Takei
Axonal regeneration in the adult mammalian central nervous system is limited in part by the non-permissive environment, including axonal growth inhibitors such as the Nogo-A protein. How the functions of these inhibitors can be blocked remains unclear. Here, we examined the role of LOTUS, an endogenous Nogo receptor antagonist, in promoting functional recovery and neural repair after spinal cord injury (SCI), as well as axonal regeneration after optic nerve crush. Wild-type untreated mice show incomplete but substantial intrinsic motor recovery after SCI...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28917662/successful-optic-nerve-regeneration-in-the-senescent-zebrafish-despite-age-related-decline-of-cell-intrinsic-and-extrinsic-response-processes
#16
Jessie Van Houcke, Ilse Bollaerts, Emiel Geeraerts, Benjamin Davis, An Beckers, Inge Van Hove, Kim Lemmens, Lies De Groef, Lieve Moons
Dysfunction of the central nervous system (CNS) in neurodegenerative diseases or after brain lesions seriously affects life quality of a growing number of elderly, since the adult CNS lacks the capacity to replace or repair damaged neurons. Despite intensive research efforts, full functional recovery after CNS disease and/or injury remains challenging, especially in an aging environment. As such, there is a rising need for an aging model in which the impact of aging on successful regeneration can be studied...
December 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28895631/-oct-angiography-of-rpe-tears-in-exudative-amd-morpohological-analysis-of-the-choriocapillaris-and-the-rpe
#17
Matthias Gutfleisch, Kai Rothaus, Marie-Louise Farecki, Henrik Faatz, Britta Heimes-Bussmann, Frederic Gunnemann, Martin Ziegler, Ioannis Papapostolou, Albrecht Lommatzsch, Daniel Pauleikoff
Background Retinal pigment epithelium (RPE) tears are a typical complication of vascular pigment epithelium detachment in age-related macular degeneration (AMD). During proactive intense anti-VEGF therapy, stabilisation or improvement of function may occur. With the new method of OCT angiography (OCT-A), retinal vessels and flow density can be quantified. This pilot study investigates changes in the choriocapillars (CC) in areas with increasing FAF in OCT following an RPE-tear. Methods In six eyes with an RPE-tear, prospectively initially and every three months thereafter, multimodal imaging was performed, including fundus autofluorescence (FAF) (HRA2, Heidelberg Engineering, Heidelberg, Deutschland) and OCT-A (RTVue XR Avanti, SSDA-Modus, Angiovue, Optovue, Freemont, CA, USA)...
September 2017: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/28894166/flavonoid-allosteric-modulation-of-mutated-visual-rhodopsin-associated-with-retinitis-pigmentosa
#18
María Guadalupe Herrera-Hernández, Eva Ramon, Cecylia S Lupala, Mercè Tena-Campos, Juan J Pérez, Pere Garriga
Dietary flavonoids exhibit many biologically-relevant functions and can potentially have beneficial effects in the treatment of pathological conditions. In spite of its well known antioxidant properties, scarce structural information is available on the interaction of flavonoids with membrane receptors. Advances in the structural biology of a specific class of membrane receptors, the G protein-coupled receptors, have significantly increased our understanding of drug action and paved the way for developing improved therapeutic approaches...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871032/klf9-and-jnk3-interact-to-suppress-axon-regeneration-in-the-adult-cns
#19
Akintomide Apara, Joana Galvao, Yan Wang, Murray Blackmore, Allison Trillo, Keiichiro Iwao, Dale P Brown, Kimberly A Fernandes, Abigail Huang, Tu Nguyen, Masoumeh Ashouri, Xiong Zhang, Peter X Shaw, Noelia J Kunzevitzky, Darcie L Moore, Richard T Libby, Jeffrey L Goldberg
Neurons in the adult mammalian CNS decrease in intrinsic axon growth capacity during development in concert with changes in Krüppel-like transcription factors (KLFs). KLFs regulate axon growth in CNS neurons including retinal ganglion cells (RGCs). Here, we found that knock-down of KLF9, an axon growth suppressor that is normally upregulated 250-fold in RGC development, promotes long-distance optic nerve regeneration in adult rats of both sexes. We identified a novel binding partner, MAPK10/JNK3 kinase, and found that JNK3 (c-Jun N-terminal kinase 3) is critical for KLF9's axon-growth-suppressive activity...
October 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28856242/3d-visualization-of-individual-regenerating-retinal-ganglion-cell-axons-reveals-surprisingly-complex-growth-paths
#20
Eric R Bray, Markus Noga, Kinjal Thakor, Yunfang Wang, Vance P Lemmon, Kevin K Park, Pantelis Tsoulfas
Retinal ganglion cells (RGCs), the sole output cells of the retina, are a heterogeneous population of neurons that project axons to visual targets in the brain. Like most CNS neurons, RGCs are considered incapable of mounting long distance axon regeneration. Using immunolabeling-enabled 3D imaging of solvent-cleared organs (iDISCO) in transgenic mice, we tracked the entire paths of individual RGC axons and show that adult RGCs are highly capable of spontaneous long-distance regeneration, even without any treatment...
July 2017: ENeuro
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