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Retinal regeneration

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https://www.readbyqxmd.com/read/28220544/prospective-purification-and-characterization-of-m%C3%A3-ller-glia-in-the-mouse-retina-regeneration-assay
#1
Patrick Schäfer, Mike O Karl
Reactive gliosis is an umbrella term for various glia functions in neurodegenerative diseases and upon injury. Specifically, Müller glia (MG) in some species readily regenerate retinal neurons to restore vision loss after insult, whereas mammalian MG respond by reactive gliosis-a heterogeneous response which frequently includes cell hypertrophy and proliferation. Limited regeneration has been stimulated in mammals, with a higher propensity in young MG, and in vitro compared to in vivo, but the underlying processes are unknown...
February 21, 2017: Glia
https://www.readbyqxmd.com/read/28212859/docosahexaenoic-acid-phospholipid-differentially-modulates-the-conformation-of-g90v-and-n55k-rhodopsin-mutants-associated-with-retinitis-pigmentosa
#2
Xiaoyun Dong, María Guadalupe Herrera-Hernández, Eva Ramon, Pere Garriga
Rhodopsin is the visual photoreceptor of the retinal rod cells that mediates dim light vision and a prototypical member of the G protein-coupled receptor superfamily. The structural stability and functional performance of rhodopsin are modulated by membrane lipids. Docosahexaenoic acid has been shown to interact with native rhodopsin but no direct evidence has been established on the effect of such lipid on the stability and regeneration of rhodopsin mutants associated with retinal diseases. The stability and regeneration of two thermosensitive mutants G90V and N55K, associated with the retinal degenerative disease retinitis pigmentosa, have been analyzed in docosohexaenoic phospholipid (1,2-didocosa-hexaenoyl-sn-glycero-3-phosphocholine; DDHA-PC) liposomes...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28198592/bone-marrow-derived-mesenchymal-stem-cells-derived-exosomes-promote-survival-of-retinal-ganglion-cells-through-mirna-dependent-mechanisms
#3
Ben Mead, Stanislav Tomarev
The loss of retinal ganglion cells (RGC) and their axons is one of the leading causes of blindness and includes traumatic (optic neuropathy) and degenerative (glaucoma) eye diseases. Although no clinical therapies are in use, mesenchymal stem cells (MSC) have demonstrated significant neuroprotective and axogenic effects on RGC in both of the aforementioned models. Recent evidence has shown that MSC secrete exosomes, membrane enclosed vesicles (30-100 nm) containing proteins, mRNA and miRNA which can be delivered to nearby cells...
February 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28194183/regulation-of-stem-cell-properties-of-m%C3%A3-ller-glia-by-jak-stat-and-mapk-signaling-in-the-mammalian-retina
#4
REVIEW
Krista M Beach, Jianbo Wang, Deborah C Otteson
In humans and other mammals, the neural retina does not spontaneously regenerate, and damage to the retina that kills retinal neurons results in permanent blindness. In contrast to embryonic stem cells, induced pluripotent stem cells, and embryonic/fetal retinal stem cells, Müller glia offer an intrinsic cellular source for regenerative strategies in the retina. Müller glia are radial glial cells within the retina that maintain retinal homeostasis, buffer ion flux associated with phototransduction, and form the blood/retinal barrier within the retina proper...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28192065/vascular-endothelial-growth-factor-a-and-leptin-expression-associated-with-ectopic-proliferation-and-retinal-dysplasia-in-zebrafish-optic-pathway-tumors
#5
Laura E Schultz, Staci L Solin, Wesley A Wierson, Janna M Lovan, Judith Syrkin-Nikolau, Deborah E Lincow, Andrew J Severin, Donald S Sakaguchi, Maura McGrail
In the central nervous system injury induces cellular reprogramming and progenitor proliferation, but the molecular mechanisms that limit regeneration and prevent tumorigenesis are not completely understood. We previously described a zebrafish optic pathway tumor model in which transgenic Tg(flk1:RFP)is18/+ adults develop nonmalignant retinal tumors. Key pathways driving injury-induced glial reprogramming and regeneration contributed to tumor formation. In this study, we examine a time course of proliferation and present new analyses of the Tg(flk1:RFP)is18/+ dysplastic retina and tumor transcriptomes...
February 13, 2017: Zebrafish
https://www.readbyqxmd.com/read/28186701/bone-marrow-derived-mesenchymal-stem-cells-derived-exosomes-promote-survival-of-retinal-ganglion-cells-through-mirna-dependent-mechanisms
#6
Ben Mead, Stanislav Tomarev
The loss of retinal ganglion cells (RGC) and their axons is one of the leading causes of blindness and includes traumatic (optic neuropathy) and degenerative (glaucoma) eye diseases. Although no clinical therapies are in use, mesenchymal stem cells (MSC) have demonstrated significant neuroprotective and axogenic effects on RGC in both of the aforementioned models. Recent evidence has shown that MSC secrete exosomes, membrane enclosed vesicles (30-100 nm) containing proteins, mRNA and miRNA which can be delivered to nearby cells...
January 26, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28185609/olfactory-ensheathing-cells-inhibit-gliosis-in-retinal-degeneration-by-down-regulation-of-the-m%C3%A3-ller-cell-notch-signaling-pathway
#7
Jing Xie, Shujia Huo, Yijian Li, Jiaman Dai, Haiwei Xu, Zheng Qin Yin
Retinal regeneration and self-repair, whether in response to injury or degenerative disease, are severely impeded by glial scar formation by Müller cells (specialized retinal macroglia). We have previously demonstrated that the activation of Müller cells and gliosis in the degenerative retina are significantly suppressed by the subretinal transplantation of a mixture of olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts. However, the underlying molecular mechanism has remained elusive. Here, we transplanted purified rat OECs into the subretinal space of pigmented Royal College of Surgeons (RCS) rats, a classic rodent model of retinal degeneration...
February 9, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28164440/effect-of-human-umbilical-cord-blood-mesenchymal-stem-cells-administered-by-intravenous-or-intravitreal-routes-on-cryo-induced-retinal-injury
#8
Eman M Mohamed, Shaimaa A Abdelrahman, Samia Hussein, Sally M Shalaby, Hala Mosaad, Ahmed M B Awad
Traumatic optic neuropathy is an important cause of severe vision loss. So, many attempts were performed to transplant stem cells systemically or locally to regenerate the injured retina. In this study, we investigated the effect of human umbilical cord blood mesenchymal stem cells (hUBMSCs) on histological structure, apoptotic, antiapoptotic, oxidant and antioxidant markers in an experimental model of cryo-induced retinal damage in mice. Forty-eight mice were included with 4 major groups; group I contained 18 mice as controls...
February 5, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28153739/the-challenge-of-regenerative-therapies-for-the-optic-nerve-in-glaucoma
#9
David J Calkins, Milos Pekny, Melissa L Cooper, Larry Benowitz
This review arose from a discussion of regenerative therapies to treat optic nerve degeneration in glaucoma at the 2015 Lasker/IRRF Initiative on Astrocytes and Glaucomatous Neurodegeneration. In addition to the authors, participants included Jonathan Crowston, Andrew Huberman, Elaine Johnson, Richard Lu, Hemai Phatnami, Rebecca Sappington, and Don Zack. Glaucoma is a neurodegenerative disease of the optic nerve, and is the leading cause of irreversible blindness worldwide. The disease progresses as sensitivity to intraocular pressure (IOP) is conveyed through the optic nerve head to distal retinal ganglion cell (RGC) projections...
January 30, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28147247/evidence-of-brdu-positive-retinal-neurons-after-application-of-an-alpha7-nicotinic-acetylcholine-receptor-agonist
#10
Mark K Webster, Cynthia A Cooley-Themm, Joseph D Barnett, Harrison B Bach, Jessica M Vainner, Sarah E Webster, Cindy L Linn
Irreversible vision loss due to disease or age is responsible for a reduced quality of life. The experiments in this study test the hypothesis that the α7 nicotinic acetylcholine receptor agonist, PNU-282987, leads to the generation of retinal neurons in an adult mammalian retina in the absence of retinal injury or exogenous growth factors. Using antibodies against BrdU, retinal ganglion cells, progenitor cells and Müller glia, the results of this study demonstrate that multiple types of retinal cells and neurons are generated after eye drop application of PNU-282987 in adult Long Evans rats in a dose-dependent manner...
January 29, 2017: Neuroscience
https://www.readbyqxmd.com/read/28131621/talkin-about-my-re-generation-the-who-of-intrinsic-retinal-stem-cells
#11
Deborah C Otteson
World-wide, two degenerative retinal diseases, glaucoma and age-related macular degeneration, are estimated to affect more than 12% of individuals over the age of 40 (Tham et al., 2014; Wong et al., 2014). Current therapies can slow progression, but cannot restore lost neurons or vision. Thus, there is increasing interest in developing strategies for therapeutic retinal regeneration. Nearly 50years of research on retinal neurogenesis and regeneration has identified Müller glia as intrinsic retinal stem cells in teleost fish...
January 25, 2017: Neuroscience
https://www.readbyqxmd.com/read/28118667/restoration-of-mesenchymal-rpe-by-transcription-factor-mediated-reprogramming
#12
Ying-Hsuan Shih, Monte J Radeke, Carolyn M Radeke, Pete J Coffey
Purpose: Transforming growth factor β-mediated epithelial-to-mesenchymal transition (EMT) is a major component of the wound healing response and a negative determinant of retinal pigment epithelium (RPE) differentiation. We have shown previously that inhibition of TGFβ signaling restored the capacity of mesenchymal RPE to differentiate; however, the potential lessens with extensive passaging. We investigated TGFβ-independent mechanisms that regulate RPE differentiation following repetitive passaging...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28096191/allosteric-modulation-of-the-substrate-specificity-of-acyl-coa-wax-alcohol-acyltransferase-2-awat2
#13
Jason M Arne, Made Airanthi K Widjaja-Adhi, Taylor Hughes, Kevin W Huynh, Josie A Silvaroli, Sylwia Chelstowska, Vera Y Moiseenkova-Bell, Marcin Golczak
The esterification of alcohols with fatty acids is a universal mechanism to form inert storage forms of sterols, di- and triacylglycerols, and retinoids. In ocular tissues, formation of retinyl esters is an essential step in the enzymatic regeneration of the visual chromophore (11-cis-retinal). Acyl-CoA wax alcohol acyltransferase 2 (AWAT2), also known as multifunctional O-acyltransferase (MFAT), is an integral membrane enzyme with a broad substrate specificity that has been shown to preferentially esterify 11-cis-retinol and thus contribute to formation of readily available pool of cis retinoids in the eye...
January 17, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28049891/development-of-cellular-and-tissue-based-products-for-retinal-regenerative-medicine
#14
Fumitaka Osakada
 Since the discovery of induced pluripotent stem cells (iPSCs) generation, much progress has been made in the fields of medical and pharmaceutical research, such as cell transplantation therapy. We have generated retinal cells and tissues, including retinal pigment epithelia (RPE), from human iPSCs. The ability to produce iPSCs from patients allows for autologous transplantation without causing immune rejection. The autologous transplantation of iPSC-derived retinal pigment epithelial sheets to a patient with age-related macular degeneration was carried out in Japan in 2014 as a first-in-human clinical study...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28049831/mobile-zinc-increases-rapidly-in-the-retina-after-optic-nerve-injury-and-regulates-ganglion-cell-survival-and-optic-nerve-regeneration
#15
Yiqing Li, Lukas Andereggen, Kenya Yuki, Kumiko Omura, Yuqin Yin, Hui-Ya Gilbert, Burcu Erdogan, Maria S Asdourian, Christine Shrock, Silmara de Lima, Ulf-Peter Apfel, Yehong Zhuo, Michal Hershfinkel, Stephen J Lippard, Paul A Rosenberg, Larry Benowitz
Retinal ganglion cells (RGCs), the projection neurons of the eye, cannot regenerate their axons once the optic nerve has been injured and soon begin to die. Whereas RGC death and regenerative failure are widely viewed as being cell-autonomous or influenced by various types of glia, we report here that the dysregulation of mobile zinc (Zn(2+)) in retinal interneurons is a primary factor. Within an hour after the optic nerve is injured, Zn(2+) increases several-fold in retinal amacrine cell processes and continues to rise over the first day, then transfers slowly to RGCs via vesicular release...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28041994/a-dominant-mutation-in-rpe65-d477g-delays-dark-adaptation-and-disturbs-the-visual-cycle-in-the-mutant-knock-in-mice
#16
Younghwa Shin, Gennadiy Moiseyev, Dibyendu Chakraborty, Jian-Xing Ma
RPE65 is an indispensable component of the retinoid visual cycle in vertebrates, through which the visual chromophore 11-cis-retinal (11-cis-RAL) is generated to maintain normal vision. Various blinding conditions in humans, such as Leber congenital amaurosis and retinitis pigmentosa (RP), are attributed to either homozygous or compound heterozygous mutations in RPE65. Herein, we investigated D477G missense mutation, an unprecedented dominant-acting mutation of RPE65 identified in patients with autosomal dominant RP...
December 30, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/28029073/exploring-optic-nerve-axon-regeneration
#17
Hong-Jiang Li, Zhao-Liang Sun, Xi-Tao Yang, Liang Zhu, Dong-Fu Feng
Traumatic optic nerve (ON) injury is a leading cause of irreversible visual impairment worldwide. To date, neither pharmacological nor surgical interventions are sufficient to halt or reverse the progression of visual loss. Axon regeneration is critical for functional recovery of vision following ON injury. After ON injury, retinal ganglion cells (RGCs) axons usually fail to regrow and instead die back, leading to the death of the RGCs and subsequently causing the functional loss of vision. However, the detailed molecular mechanisms underlying axon regeneration after ON injury remain poorly understood...
December 27, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/28017835/aav-mediated-transfer-of-rhoa-shrna-and-cntf-promotes-retinal-ganglion-cell-survival-and-axon-regeneration
#18
Ling-Ping Cen, Jia-Jian Liang, Jian-Huan Chen, Alan R Harvey, Tsz Kin Ng, Mingzhi Zhang, Chi Pui Pang, Qi Cui, You-Ming Fan
The aim of the present study was to determine whether adeno-associated viral vector (AAV) mediated transfer of ciliary neurotrophic factor (CNTF) and RhoA shRNA has additive effects on promoting the survival and axon regeneration of retinal ganglion cells (RGCs) after optic nerve crush (ONC). Silencing effects of AAV-RhoA shRNA were confirmed by examining neurite outgrowth in PC12 cells, and by quantifying RhoA expression levels with western blotting. Young adult Fischer rats received an intravitreal injection of (i) saline, (ii) AAV green fluorescent protein (GFP), (iii) AAV-CNTF, (iv) AAV-RhoA shRNA, or (v) a combination of both AAV-CNTF and AAV-RhoA shRNA...
December 23, 2016: Neuroscience
https://www.readbyqxmd.com/read/28011153/wnt-signaling-promotes-axonal-regeneration-following-optic-nerve-injury-in-the-mouse
#19
Amit K Patel, Kevin K Park, Abigail S Hackam
Adult mammalian CNS axons generally do not regenerate, creating an obstacle to effective repair and recovery after neuronal injury. The canonical Wnt/β-catenin signaling pathway is an essential signal transduction cascade that regulates axon growth and neurite extension in the developing mammalian embryo. In this study, we investigated whether a Wnt/β-catenin signaling activator could be repurposed to induce regeneration in the adult CNS after axonal injury. We used a retinal ganglion cell (RGC) axon crush injury model in a transgenic Wnt reporter mouse, and intravitreal injections were used to deliver Wnt3a or saline to the RGC cell bodies within the retina...
February 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/28009347/an-integrin-approach-to-axon-regeneration
#20
J W Fawcett
Axon regeneration in the CNS is blocked by inhibitory molecules in the environment and by a developmental loss of regenerative potential in CNS axons. Axon growth is a specialized form of cell migration, and for any cell to migrate there must be an adhesion molecule at the growth tip that recognizes a ligand in the environment, and which is linked to signaling and cytoskeletal mechanisms. The reasons for this loss of regenerative ability in CNS axons are several, but important contributors are the developmental loss of integrins that recognize ligands in the mature CNS environment, and selective trafficking of integrins and other molecules to exclude them from axons and direct them to dendrites...
February 2017: Eye
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