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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/28552606/differentiation-and-transplantation-of-embryonic-stem-cell-derived-cone-photoreceptors-into-a-mouse-model-of-end-stage-retinal-degeneration
#4
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/28542257/long-term-results-after-limited-macular-translocation-surgery-for-wet-age-related-macular-degeneration
#5
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/28516002/transplantation-of-human-embryonic-stem-cell-derived-retinal-cells-into-the-subretinal-space-of-a-non-human-primate
#6
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/28511069/ischaemic-preconditioning-current-knowledge-and-potential-future-applications-after-30-years-of-experience
#7
REVIEW
Karolina Stokfisz, Anna Ledakowicz-Polak, Maciej Zagorski, Marzenna Zielinska
Ischaemic preconditioning (IPC) phenomenon has been known for thirty years. During that time several studies showed that IPC provided by brief ischaemic and reperfusion episodes prior to longer ischaemia can bestow a protective effect to both preconditioned and also remote organs. IPC affecting remote organs is called remote ischaemic preconditioning. Initially, most IPC studies were focused on enhancing myocardial resistance to subsequent ischaemia and reperfusion injury. However, preconditioning was found to be a universal phenomenon and was observed in various organs and tissues including the heart, liver, brain, retina, kidney, skeletal muscles and intestine...
May 13, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28499053/a-modified-perfluoro-n-octane-assisted-autologous-internal-limiting-membrane-transplant-for-failed-macular-hole-reintervention-a-case-series
#8
Sengul Ozdek, Prabu Baskaran, Levent Karabas, Pedro Pereira Neves
The authors describe a modified perfluoro-n-octane (PFO)-assisted autologous internal limiting membrane (ILM) transplantation technique for macular hole (MH) reintervention and present results from a series of 11 patients. The authors harvested a free ILM flap and transplanted it into the MH under a PFO bubble. The time at which PFO is injected, the extent of coverage of PFO, and the sequence of fluid-air exchange (FAE) are crucial to overcome previously described technical difficulties of relieving the flap from forceps, stabilizing the flap into the MH, and prevention of flap dislodgement during FAE...
May 1, 2017: Ophthalmic Surgery, Lasers & Imaging Retina
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
#9
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/28433627/docosahexaenoic-acid-promotes-differentiation-of-photoreceptor-cells-in-three-dimensional-neural-retinas
#10
Eisuke Arai, Vipul M Parmar, Bhubanananda Sahu, Lindsay Perusek, Tanu Parmar, Akiko Maeda
Retinal tissues generated from human pluripotent stem cells can be an excellent tool for investigating pathogenesis of retinal diseases and developing new pharmacologic therapies. Moreover, patient derived retinal tissues could allow for retinal transplantation therapy for degenerative retinal diseases. However, obtaining retinal tissues with matured photoreceptor outer segments, which are essential for photoreceptor functions, is currently challenging. Here we investigated the effects of docosahexaenoic acid (DHA) for maturation of photoreceptor outer segments at the late stage and visual chromophore analog, 9-cis-retinal for the early stage of differentiation to three-dimensional (3D)-retinal tissues from human embryonic stem cells (hESCs), respectively...
April 19, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28412300/mechanisms-of-retinal-damage-after-ocular-alkali-burns
#11
Eleftherios I Paschalis, Chengxin Zhou, Fengyang Lei, Nathan Scott, Vassiliki Kapoulea, Marie-Claude Robert, Demetrios Vavvas, Reza Dana, James Chodosh, Claes H Dohlman
Alkali burns to the eye constitute a leading cause of worldwide blindness. In recent case series, corneal transplantation revealed unexpected damage to the retina and optic nerve in chemically burned eyes. We investigated the physical, biochemical, and immunological components of retinal injury after alkali burn and explored a novel neuroprotective regimen suitable for prompt administration in emergency departments. Thus, in vivo pH, oxygen, and oxidation reduction measurements were performed in the anterior and posterior segment of mouse and rabbit eyes using implantable microsensors...
June 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28411269/novel-regulatory-mechanisms-for-the-soxc-transcriptional-network-required-for-visual-pathway-development
#12
Kun-Che Chang, Jonathan Hertz, Xiong Zhang, Xiao-Lu Jin, Peter Shaw, Brooke A Derosa, Janet Y Li, Praseeda Venugopalan, Daniel A Valenzuela, Roshni D Patel, Kristina R Russano, Shomoukh A Alshamekh, Catalina Sun, Kevin Tenerelli, Chenyi Li, Dmitri Velmeshev, Yuyan Cheng, Timothy M Boyce, Alexandra Dreyfuss, Mohammed S Uddin, Kenneth J Muller, Derek M Dykxhoorn, Jeffrey L Goldberg
What pathways specify retinal ganglion cell (RGC) fate in the developing retina? Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is required for RGC differentiation and for optic nerve formation in mice in vivo, and is sufficient to differentiate human induced pluripotent stem cells into electrophysiologically active RGCs. These data place Sox4 downstream of RE1 silencing transcription factor in regulating RGC fate, and further describe a newly identified, Sox4-regulated site for post-translational modification with small ubiquitin-related modifier (SUMOylation) in Sox11, which suppresses Sox11's nuclear localization and its ability to promote RGC differentiation, providing a mechanism for the SoxC familial compensation observed here and elsewhere in the nervous system...
May 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28402835/ipsc-derived-retina-transplants-improve-vision-in-rd1-end-stage-retinal-degeneration-mice
#13
Michiko Mandai, Momo Fujii, Tomoyo Hashiguchi, Genshiro A Sunagawa, Shin-Ichiro Ito, Jianan Sun, Jun Kaneko, Junki Sho, Chikako Yamada, Masayo Takahashi
No abstract text is available yet for this article.
April 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28395300/noninvasive-quantification-of-retinal-microglia-using-widefield-autofluorescence-imaging
#14
Despina Kokona, Nadia Schneider, Helena Giannakaki-Zimmermann, Joel Jovanovic, Andreas Ebneter, Martin Zinkernagel
Purpose: To validate widefield autofluorescence (AF) in vivo imaging of the retina in mice expressing green fluorescent protein (gfp) in microglia, and to monitor retinal microglia reconstitution in vivo after lethal irradiation and bone marrow transplantation. Methods: Transgenic Cx3cr1gfp/gfp and wildtype Balb/c mice were used in this study. A confocal scanning laser ophthalmoscope was used for AF imaging with a 55° and a widefield 102° lens. Intrasession reproducibility was assessed for each lens...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28370284/induced-retro-differentiation-of-human-retinal-pigment-epithelial-cells-on-polyhema
#15
Fatemeh Nazemroaya, Zahra-Soheila Soheili, Shahram Samiei, Abdolkhalegh Deezagi, Hamid Ahmadieh, Malihe Davari, Razeih Heidari, Abouzar Bagheri, Shamila Darvishalipour-Astaneh
Retinal pigment epithelium (RPE) cells represent a great potential to rescue degenerated cells of the damaged retina. Activation of the virtually plastic properties of RPE cells may aid in recovery of retinal degenerative disorders without the need for entire RPE sheet transplantation. Poly (2-hydroxyethyl methacrylate)(PolyHEMA) is one of the most important hydrogels in the biomaterials world. This hydrophobic polymer does not normally support attachment of mammalian cells. In the current study we investigated the effect of PolyHEMA as a cell culture substrate on the growth, differentiation and plasticity of hRPE cells...
March 29, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28355662/-photoreceptor-transplantation-into-the-degenerative-retina
#16
O Borsch, T Santos-Ferreira, M Ader
Vision impairment and blindness due to photoreceptor loss represents one of the major causes for disability in industrialized societies. Whereas rod photoreceptors allow vision under dim light conditions, cone photoreceptors provide high-acuity vision in daylight conditions and color detection. Several therapeutic strategies are currently developed to repair vision loss, including cell-based interventions. Within the last decade, major progress regarding the replacement of photoreceptors by transplantation has been made in pre-clinical animal models...
March 2017: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/28351499/retina-tissue-engineering-by-conjunctiva-mesenchymal-stem-cells-encapsulated-in-fibrin-gel-hypotheses-on-novel-approach-to-retinal-diseases-treatment
#17
Mostafa Soleimannejad, Somayeh Ebrahimi-Barough, Samad Nadri, Mohammad Riazi-Esfahani, Masoud Soleimani, Seyed Mohammad Tavangar, Jafar Ai
BACKGROUND: Retinitis pigmentosa (RP) and age related macular degeneration (AMD) are two retinal diseases that progress by photoreceptor cells death. In retinal transplantation studies, stem and progenitor cells inject into the sub retinal space or vitreous and then these cells can be migrate to the site of retinal degeneration and locate in the host retina and restitute vision. PRESENTATION OF THE HYPOTHESIS: Our hypothesis suggests that using human conjunctiva stem cells (as the source for increasing the number of human stem cells progenitor cells in retina dysfunction diseases) with fibrin gel and also assessing its relating in vitro (cellular and molecular processes) and in vivo (vision tests and pathology) could be a promising strategy for treatment of AMD and RP disorders...
April 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28322827/structural-divergence-of-essential-triad-ribbon-synapse-proteins-among-placental-mammals-implications-for-preclinical-trials-in-photoreceptor-transplantation-therapy
#18
Christopher R J Laver, Joanne A Matsubara
As photoreceptor transplantation rapidly moves closer to the clinic, verifying graft efficacy in animal models may have unforeseen xenogeneic barriers. Although photoreceptor transplants have most convincingly exhibited functional synaptogenesis in conspecific studies, such evidence (while ruling out false-positives due to: viral graft labeling, fusion/cytosolic transfer, or neuroprotection) has not yet been shown for discordant xenografts. From this, a fundamental question should be raised: is useful xenosynaptogenesis likely between human photoreceptors and mouse retina? The triad ribbon synapse (TRS) that would normally form is unique and contains trans-synaptic proteins essential to its formation and function...
March 18, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28321468/hyperglycaemic-memory-affects-the-neurovascular-unit-of-the-retina-in-a-diabetic-mouse-model
#19
Patrick Friedrichs, Andrea Schlotterer, Carsten Sticht, Matthias Kolibabka, Paulus Wohlfart, Axel Dietrich, Thomas Linn, Grietje Molema, Hans-Peter Hammes
AIMS/HYPOTHESIS: The aim of this study was to evaluate damage to the neurovascular unit in a mouse model of hyperglycaemic memory. METHODS: A streptozotocin-induced mouse model of diabetes (C57BL/6J background) received insulin-releasing pellets and pancreatic islet-cell transplantation. Damage to the neurovascular unit was studied by quantitative retinal morphometry for microvascular changes and microarray analysis, with subsequent functional annotation clustering, for changes of the retinal genome...
March 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28298640/combined-transplantation-of-human-mesenchymal-stem-cells-and-human-retinal-progenitor-cells-into-the-subretinal-space-of-rcs-rats
#20
Linghui Qu, Lixiong Gao, Haiwei Xu, Ping Duan, Yuxiao Zeng, Yong Liu, Zheng Qin Yin
Retinitis pigmentosa (RP) is one of hereditary retinal diseases characterized by the loss of photoreceptors. Cell transplantation has been clinically applied to treat RP patients. Human retinal progenitor cells (HRPCs) and human bone marrow-derived mesenchymal stem cells (HBMSCs) are the two commonly and practically used stem cells for transplantation. Since combined transplantation could be a promising way to integrate the advantages of both stem cell types, we transplanted HRPCs and HBMSCs into the subretinal space (SRS) of Royal College of Surgeons (RCS) rats...
March 15, 2017: Scientific Reports
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