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Retina, stem cells

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https://www.readbyqxmd.com/read/28636206/retinal-vascular-injuries-and-intravitreal-human-embryonic-stem-cell-derived-haemangioblasts
#1
Jin-Da Wang, Ying An, Jing-Shang Zhang, Xiu-Hua Wan, Wei Zhang, Robert Lanza, Shi-Jiang Lu, Jost B Jonas, Liang Xu
OBJECTIVE: To investigate whether intravitreally applied haemangioblasts (HB) derived from human embryonic stem cells (hESCs) are helpful for the repair of vascular damage caused in animals by an oxygen-induced retinopathy (OIR), by an induced diabetic retinopathy (DR) or by an induced retinal ischaemia with subsequent reperfusion. METHODS: Human embryonic stem cell-derived HBs were transplanted intravitreally into C57BL/6J mice (OIR model), into male Wistar rats with an induced DR and into male Wistar rats undergoing induced retinal ischaemia with subsequent reperfusion...
June 21, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28626601/long-term-efficacy-of-gmp-grade-xeno-free-hesc-derived-rpe-cells-following-transplantation
#2
Trevor J McGill, Osnat Bohana-Kashtan, Jonathan W Stoddard, Michael D Andrews, Neelay Pandit, Lior R Rosenberg-Belmaker, Ofer Wiser, Limor Matzrafi, Eyal Banin, Benjamin Reubinoff, Nir Netzer, Charles Irving
PURPOSE: Retinal pigment epithelium (RPE) dysfunction underlies the retinal degenerative process in age-related macular degeneration (AMD), and thus RPE cell replacement provides an optimal treatment target. We characterized longitudinally the efficacy of RPE cells derived under xeno-free conditions from clinical and xeno-free grade human embryonic stem cells (OpRegen) following transplantation into the subretinal space of Royal College of Surgeons (RCS) rats. METHODS: Postnatal (P) day 20 to 25 RCS rats (n = 242) received a single subretinal injection of 25,000 (low)-, 100,000 (mid)-, or 200,000 (high)-dose xeno-free RPE cells...
June 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28619647/using-crispr-cas9-to-generate-gene-corrected-autologous-ipscs-for-the-treatment-of-inherited-retinal-degeneration
#3
Erin R Burnight, Manav Gupta, Luke A Wiley, Kristin R Anfinson, Audrey Tran, Robinson Triboulet, Jeremy M Hoffmann, Darcey L Klaahsen, Jeaneen L Andorf, Chunhua Jiao, Elliott H Sohn, Malavika K Adur, Jason W Ross, Robert F Mullins, George Q Daley, Thorsten M Schlaeger, Edwin M Stone, Budd A Tucker
Patient-derived induced pluripotent stem cells (iPSCs) hold great promise for autologous cell replacement. However, for many inherited diseases, treatment will likely require genetic repair pre-transplantation. Genome editing technologies are useful for this application. The purpose of this study was to develop CRISPR-Cas9-mediated genome editing strategies to target and correct the three most common types of disease-causing variants in patient-derived iPSCs: (1) exonic, (2) deep intronic, and (3) dominant gain of function...
June 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28616037/correlation-between-photoreceptor-injury-regeneration-and-behavior-in-a-zebrafish-model
#4
Ya-Jie Wang, Shi-Jiao Cai, Jian-Lin Cui, Yang Chen, Xin Tang, Yu-Hao Li
Direct exposure to intensive visible light can lead to solar retinopathy, including macular injury. The signs and symptoms include central scotoma, metamorphopsia, and decreased vision. However, there have been few studies examining retinal injury due to intensive light stimulation at the cellular level. Neural network arrangements and gene expression patterns in zebrafish photoreceptors are similar to those observed in humans, and photoreceptor injury in zebrafish can induce stem cell-based cellular regeneration...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28612282/probing-of-peripheral-blood-mononuclear-cells-anchoring-on-tnf-alpha-challenged-vascular-endothelia-in-an-in-vitro-model-of-the-retinal-microvascular
#5
Yuan Li, Yao Lu, Qiong Chen, Yuejun Kang, Ling Yu
Retinopathy is a complication of diabetes that affects the eyes; it stems from damage to the microvasculature of the retina and eventually compromises vision. The diagnosis of retinopathy is difficult to make because there are no early symptoms or warning signs. Dysfunction of the retina's microvascular networks is believed to be associated with inflammatory cytokines and tumor necrosis factor alpha (TNF-α). To investigate the effect of these cytokines, such as TNF-α, a polydimethylsiloxane (PDMS)/glass hydride microfluidic device reflecting the physiological structure of the retina's microvasculature was developed...
September 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28596937/harnessing-the-potential-of-human-pluripotent-stem-cells-and-gene-editing-for-the-treatment-of-retinal-degeneration
#6
REVIEW
Patrick Ovando-Roche, Anastasios Georgiadis, Alexander J Smith, Rachael A Pearson, Robin R Ali
PURPOSE OF REVIEW: A major cause of visual disorders is dysfunction and/or loss of the light-sensitive cells of the retina, the photoreceptors. To develop better treatments for patients, we need to understand how inherited retinal disease mutations result in the dysfunction of photoreceptors. New advances in the field of stem cell and gene editing research offer novel ways to model retinal dystrophies in vitro and present opportunities to translate basic biological insights into therapies...
2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28577895/sox2-regulates-m%C3%A3-ller-glia-reprogramming-and-proliferation-in-the-regenerating-zebrafish-retina-via-lin28-and-ascl1a
#7
Ryne A Gorsuch, Manuela Lahne, Clare E Yarka, Michael E Petravick, Jingling Li, David R Hyde
Sox2 is a well-established neuronal stem cell-associated transcription factor that regulates neural development and adult neurogenesis in vertebrates, and is one of the critical genes used to reprogram differentiated cells into induced pluripotent stem cells. We examined if Sox2 was involved in the early reprogramming-like events that Müller glia undergo as they upregulate many pluripotency- and neural stem cell-associated genes required for proliferation in light-damaged adult zebrafish retinas. In the undamaged adult zebrafish retina, Sox2 is expressed in Müller glia and a subset of amacrine cells, similar to other vertebrates...
May 31, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28575952/biocompatibility-and-neurotoxicity-of-magnesium-alloys-potentially-used-for-neural-repairs
#8
Jianjun Fei, Xiaoxiao Wen, Xiao Lin, Saijilafu, Weihua Wang, Olga Ren, Xinjian Chen, Lili Tan, Ke Yang, Huilin Yang, Lei Yang
Nerve injury, especially the large-size nerve damage, is a serious problem affecting millions of people. Entubulation of two ends of the injured nerve by using an implantable device, e.g., nerve guidance conduit (NGC), to guide the regeneration of nerve tissue is a promising approach for treating the large-size nerve defect. Magnesium (Mg) and its alloys are biodegradable, conductive, and own good mechanical properties. Mg(2+) ion, one of the main degradation products of Mg and its alloys, was reported to promote the proliferation of neural stem cells and their neurite production...
September 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28575309/nonhuman-primate-studies-to-advance-vision-science-and-prevent-blindness
#9
Michael J Mustari
Most primate behavior is dependent on high acuity vision. Optimal visual performance in primates depends heavily upon frontally placed eyes, retinal specializations, and binocular vision. To see an object clearly its image must be placed on or near the fovea of each eye. The oculomotor system is responsible for maintaining precise eye alignment during fixation and generating eye movements to track moving targets. The visual system of nonhuman primates has a similar anatomical organization and functional capability to that of humans...
May 31, 2017: ILAR Journal
https://www.readbyqxmd.com/read/28552606/differentiation-and-transplantation-of-embryonic-stem-cell-derived-cone-photoreceptors-into-a-mouse-model-of-end-stage-retinal-degeneration
#10
Kamil Kruczek, Anai Gonzalez-Cordero, Debbie Goh, Arifa Naeem, Mindaugas Jonikas, Samuel J I Blackford, Magdalena Kloc, Yanai Duran, Anastasios Georgiadis, Robert D Sampson, Ryea N Maswood, Alexander J Smith, Sarah Decembrini, Yvan Arsenijevic, Jane C Sowden, Rachael A Pearson, Emma L West, Robin R Ali
The loss of cone photoreceptors that mediate daylight vision represents a leading cause of blindness, for which cell replacement by transplantation offers a promising treatment strategy. Here, we characterize cone differentiation in retinas derived from mouse embryonic stem cells (mESCs). Similar to in vivo development, a temporal pattern of progenitor marker expression is followed by the differentiation of early thyroid hormone receptor β2-positive precursors and, subsequently, photoreceptors exhibiting cone-specific phototransduction-related proteins...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28548249/m%C3%A3-ller-glial-cell-reactivation-in-xenopus-models-of-retinal-degeneration
#11
Rahul Langhe, Albert Chesneau, Gabriele Colozza, Magdalena Hidalgo, Divya Ail, Morgane Locker, Muriel Perron
A striking aspect of tissue regeneration is its uneven distribution among different animal classes, both in terms of modalities and efficiency. The retina does not escape the rule, exhibiting extraordinary self-repair properties in anamniote species but extremely limited ones in mammals. Among cellular sources prone to contribute to retinal regeneration are Müller glial cells, which in teleosts have been known for a decade to re-acquire a stem/progenitor state and regenerate retinal neurons following injury...
August 2017: Glia
https://www.readbyqxmd.com/read/28542257/long-term-results-after-limited-macular-translocation-surgery-for-wet-age-related-macular-degeneration
#12
Hisaaki Oshima, Takeshi Iwase, Kohei Ishikawa, Kentaro Yamamoto, Hiroko Terasaki
PURPOSE: To evaluate the long-term results of limited macular translocation (LMT) surgery with radial chorioscleral outfolding in patients with wet age-related macular degeneration (AMD) and subfoveal choroidal neovascularization (CNV). In addition, to identify the factors associated with the final best-corrected visual acuity (BCVA). METHODS: The medical records of 20 eyes of 20 consecutive patients (65.2±9.8 years) who had undergone LMT for the treatment of wet AMD and were followed for at least 5 years, were reviewed...
2017: PloS One
https://www.readbyqxmd.com/read/28523456/bone-marrow-mesenchymal-stem-cell-administration-significantly-improves-outcome-after-retinal-ischemia-in-rats
#13
Biji Mathew, Jacqueline N Poston, John C Dreixler, Leianne Torres, Jasmine Lopez, Ruth Zelkha, Irina Balyasnikova, Maciej S Lesniak, Steven Roth
PURPOSE: Ischemia-associated retinal degeneration is one of the leading causes of vision loss, and to date, there are no effective treatment options. We hypothesized that delayed injection of bone-marrow stem cells (BMSCs) 24 h after the onset of ischemia could effectively rescue ischemic retina from its consequences, including apoptosis, inflammation, and increased vascular permeability, thereby preventing retinal cell loss. METHODS: Retinal ischemia was induced in adult Wistar rats by increasing intraocular pressure (IOP) to 130-135 mmHg for 55 min...
May 18, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28516002/transplantation-of-human-embryonic-stem-cell-derived-retinal-cells-into-the-subretinal-space-of-a-non-human-primate
#14
Jennifer R Chao, Deepak A Lamba, Todd R Klesert, Anna La Torre, Akina Hoshino, Russell J Taylor, Anu Jayabalu, Abbi L Engel, Thomas H Khuu, Ruikang K Wang, Maureen Neitz, Jay Neitz, Thomas A Reh
PURPOSE: Previous studies have demonstrated the ability of retinal cells derived from human embryonic stem cells (hESCs) to survive, integrate into the host retina, and mediate light responses in murine mouse models. Our aim is to determine whether these cells can also survive and integrate into the retina of a nonhuman primate, Saimiri sciureus, following transplantation into the subretinal space. METHODS: hESCs were differentiated toward retinal neuronal fates using our previously published technique and cultured for 60 to 70 days...
May 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28504201/cilia-the-sensory-antennae-in-the-eye
#15
REVIEW
Helen May-Simera, Kerstin Nagel-Wolfrum, Uwe Wolfrum
Cilia are hair-like projections found on almost all cells in the human body. Originally believed to function merely in motility, the function of solitary non-motile (primary) cilia was long overlooked. Recent research has demonstrated that primary cilia function as signalling hubs that sense environmental cues and are pivotal for organ development and function, tissue hoemoestasis, and maintenance of human health. Cilia share a common anatomy and their diverse functional features are achieved by evolutionarily conserved functional modules, organized into sub-compartments...
May 11, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28489788/cytomegalovirus-retinitis-in-a-patient-with-secondary-acute-lymphosarcoma-leukemia-undergoing-allogeneic-hematopoietic-stem-cell-transplantation-a-rare-case-report-a-care-compliant-article
#16
Ning Zhao, Lei Liu, Junjie Xu
RATIONALE: Cytomegalovirus (CMV) retinitis is a common opportunistic infection in immunocompromised patients, which may lead to blindness. CMV retinitis is not an uncommon infectious disease in patients with immune regulatory abnormalities, for example, human immunodeficiency virus (HIV) patients. However, CMV retinitis in a patient with acute lymphosarcoma leukemia (ALL) undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) phase is very rare. PATIENT CONCERNS: A case of CMV retinitis in a patient receiving immunosuppressive therapy as a part of ALL allogeneic HSCT is described including the pathogenesis, clinical signs, and therapy...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28486987/progress-of-stem-progenitor-cell-based-therapy-for-retinal-degeneration
#17
REVIEW
Zhimin Tang, Yi Zhang, Yuyao Wang, Dandan Zhang, Bingqiao Shen, Min Luo, Ping Gu
Retinal degeneration (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa, is one of the leading causes of blindness. Presently, no satisfactory therapeutic options are available for these diseases principally because the retina and retinal pigmented epithelium (RPE) do not regenerate, although wet AMD can be prevented from further progression by anti-vascular endothelial growth factor therapy. Nevertheless, stem/progenitor cell approaches exhibit enormous potential for RD treatment using strategies mainly aimed at the rescue and replacement of photoreceptors and RPE...
May 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28472656/the-dynamic-epigenetic-landscape-of-the-retina-during-development-reprogramming-and-tumorigenesis
#18
Issam Aldiri, Beisi Xu, Lu Wang, Xiang Chen, Daniel Hiler, Lyra Griffiths, Marc Valentine, Abbas Shirinifard, Suresh Thiagarajan, Andras Sablauer, Marie-Elizabeth Barabas, Jiakun Zhang, Dianna Johnson, Sharon Frase, Xin Zhou, John Easton, Jinghui Zhang, Elaine R Mardis, Richard K Wilson, James R Downing, Michael A Dyer
In the developing retina, multipotent neural progenitors undergo unidirectional differentiation in a precise spatiotemporal order. Here we profile the epigenetic and transcriptional changes that occur during retinogenesis in mice and humans. Although some progenitor genes and cell cycle genes were epigenetically silenced during retinogenesis, the most dramatic change was derepression of cell-type-specific differentiation programs. We identified developmental-stage-specific super-enhancers and showed that most epigenetic changes are conserved in humans and mice...
May 3, 2017: Neuron
https://www.readbyqxmd.com/read/28469643/impacts-of-the-retinal-environment-and-photoreceptor-type-on-functional-regeneration
#19
REVIEW
Michèle G DuVal, W Ted Allison
Retinal regeneration is a promising central nervous system (CNS) target amongst the various stem cell therapy pursuits, due to its accessibility for manipulation and its disposition towards longitudinal monitoring of treatment safety and efficacy. We offer our perspective on current hurdles towards functional regeneration of cone photoreceptors. Cones are key: For patients suffering vision loss, cone photoreceptors are a required cellular component to restoring daytime vision, colour vision, and high acuity vision...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28465291/bipotent-progenitors-as-embryonic-origin-of-retinal-stem-cells
#20
Xia Tang, Jianan Gao, Xinling Jia, Wencao Zhao, Yijie Zhang, Weijun Pan, Jie He
In lower vertebrates, retinal stem cells (RSCs) capable of producing all retinal cell types are a resource for retinal tissue growth throughout life. However, the embryonic origin of RSCs remains largely elusive. Using a Zebrabow-based clonal analysis, we characterized the RSC niche in the ciliary marginal zone of zebrafish retina and illustrate that blood vessels associated with RSCs are required for the maintenance of actively proliferating RSCs. Full lineage analysis of RSC progenitors reveals lineage patterns of RSC production...
June 5, 2017: Journal of Cell Biology
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