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Retinal stem cells

Alan D Marmorstein, Adiv A Johnson, Lori A Bachman, Cynthia Andrews-Pfannkoch, Travis Knudsen, Benjamin J Gilles, Matthew Hill, Jarel K Gandhi, Lihua Y Marmorstein, Jose S Pulido
Autosomal recessive bestrophinopathy (ARB) is caused by mutations in the gene BEST1 which encodes bestrophin 1 (Best1), an anion channel expressed in retinal pigment epithelial (RPE) cells. It has been hypothesized that ARB represents the human null phenotype for BEST1 and that this occurs due to nonsense mediated decay (NMD). To test this hypothesis, we generated induced pluripotent stem cells (iPSCs) from a patient with ARB and her parents. After differentiation to retinal pigment epithelial (iPSC-RPE) cells, both BEST1 mRNA and Best1 protein expression were compared to controls...
March 14, 2018: Scientific Reports
Yingqian Peng, Edouard Baulier, Yifeng Ke, Alejandra Young, Novruz B Ahmedli, Steven D Schwartz, Debora B Farber
Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse embryonic stem cell-released EVs (mESEVs) are able to transfer their content to different target retinal cells, inducing morphological and biochemical changes in them. The main objective of this paper is to characterize EVs derived from human embryonic stem cells (hESEVs) and investigate the effects that they have on cultured retinal glial, progenitor Müller cells, which are known to give rise to retinal neurons under specific conditions...
2018: PloS One
Jane Cho, Nicole Siegel, Manju L Subramanian, Howard Ying, Steven Ness
PURPOSE: To describe a case of neovascular glaucoma from cytomegalovirus (CMV) retinitis in a human immunodeficiency virus-negative patient with immunosuppression after stem-cell transplant for multiple myeloma. METHODS: Retrospective case report. RESULTS: A 71-year-old man on monthly infusion of daratumumab for multiple myeloma after stem-cell transplant presenting with a 2-week history of floaters, photophobia, and blurry vision was found to have polymerase chain reaction-confirmed CMV retinitis associated with diffuse occlusive vasculitis...
March 12, 2018: Retinal Cases & Brief Reports
Wen-Li Deng, Mei-Ling Gao, Xin-Lan Lei, Ji-Neng Lv, Huan Zhao, Kai-Wen He, Xi-Xi Xia, Ling-Yun Li, Yu-Chen Chen, Yan-Ping Li, Deng Pan, Tian Xue, Zi-Bing Jin
Retinitis pigmentosa (RP) is an irreversible, inherited retinopathy in which early-onset nyctalopia is observed. Despite the genetic heterogeneity of RP, RPGR mutations are the most common causes of this disease. Here, we generated induced pluripotent stem cells (iPSCs) from three RP patients with different frameshift mutations in the RPGR gene, which were then differentiated into retinal pigment epithelium (RPE) cells and well-structured retinal organoids possessing electrophysiological properties. We observed significant defects in photoreceptor in terms of morphology, localization, transcriptional profiling, and electrophysiological activity...
February 28, 2018: Stem Cell Reports
Lu Wang, Daniel Hiler, Beisi Xu, Issam AlDiri, Xiang Chen, Xin Zhou, Lyra Griffiths, Marc Valentine, Abbas Shirinifard, András Sablauer, Suresh Thiagarajan, Marie-Elizabeth Barabas, Jiakun Zhang, Dianna Johnson, Sharon Frase, Michael A Dyer
Diverse cell types can be reprogrammed into pluripotent stem cells by ectopic expression of Oct4 (Pou5f1), Klf4, Sox3, and Myc. Many of these induced pluripotent stem cells (iPSCs) retain memory, in terms of DNA methylation and histone modifications (epigenetic memory), of their cellular origins, and this may bias subsequent differentiation. Neurons are difficult to reprogram, and there has not been a systematic side-by-side characterization of reprogramming efficiency or epigenetic memory across different neuronal subtypes...
March 6, 2018: Cell Reports
Jacqueline M Roberts, Monica L Vetter
The use of retinal organoids requires efficient differentiation from induced pluripotent stem cells (iPSCs). In this issue of Cell Reports, Wang et al. (2018) examine how the chromatin landscape after iPSC programming predicts their ability to differentiate into retinal tissue.
March 6, 2018: Cell Reports
Shangli Ji, Saiyue Lin, Jiansu Chen, Xinping Huang, Chih-Chang Wei, Zhiyuan Li, Shibo Tang
PURPOSE: The purpose of this study is to investigate the potential therapeutic benefits of intravitreally transplanted human umbilical cord mesenchymal stem cells (UC-MSCs) in an animal model of microbead-injection-induced ocular hypertension (OHT). METHODS: UC-MSCs were isolated from human umbilical cords and then cultured. The OHT model was induced via intracameral injection of polystyrene microbeads in Sprague-Dawley adult rat eyes. Fifty-four healthy adult rats were randomly divided into three groups: normal control, OHT model treated with intravitreal transplantation of UC-MSCs, or phosphate-buffered saline (PBS)...
March 5, 2018: Current Eye Research
Valeria Chichagova, Dean Hallam, Joseph Collin, Darin Zerti, Birthe Dorgau, Majed Felemban, Majlinda Lako, David H Steel
Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process...
March 5, 2018: Eye
Ling-Ping Cen, Tsz Kin Ng, Jia-Jian Liang, Xi Zhuang, Xiaowu Yao, Gary Hin-Fai Yam, Haoyu Chen, Herman S Cheung, Mingzhi Zhang, Chi Pui Pang
Optic neuropathies are the leading cause of irreversible blindness and visual impairment in the developed countries, affecting more than 80 million people worldwide. While most optic neuropathies have no effective treatment, there is intensive research on retinal ganglion cell (RGC) protection and axon regeneration. We previously demonstrated potential of human periodontal ligament-derived stem cells (PDLSCs) for retinal cell replacement. Here, we report the neuroprotective effect of human PDLSCs to ameliorate RGC degeneration and promote axonal regeneration after optic nerve crush (ONC) injury...
February 24, 2018: Stem Cells
Qian Gao, Wenhao Zhang, Lifang Ma, Xu Li, Haisong Wang, Yanni Li, Remo Freimann, Yang Yu, Ling Shuai, Anton Wutz
Haploid cells facilitate genetic screening of recessive mutations for a single set of chromosomes. Haploid embryonic stem cells (haESCs) have been achieved in several species and widely utilized in genetic screens. The fact that haESCs undergo substantial diploidization during differentiation has limited the screening to other haploid cell types. Here, we report a method to establish haploid neural stem cells (haNSCs) by selection for a Pax6 reporter. We inserted a green fluorescence protein (GFP) marker gene by homologous recombination into the Pax6 locus of a haESC line...
February 22, 2018: Stem Cells and Development
Takehito Iwase, Hirotaka Yokouchi, Sonoko Misawa, Toshiyuki Oshitari, Takayuki Baba, Satoshi Kuwabara, Shuichi Yamamoto
The authors present findings in a 39-year-old man with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome with bilateral optic disc oedema. He was successfully treated with bortezomib and dexamethasone followed by autologous peripheral blood stem cell transplantation. The peripapillary retinal thickness was reduced in the optical coherence tomographic (OCT) images along with a decrease of the serum vascular endothelial growth factor (VEGF) levels. The authors recommend OCT to monitor the changes in the signs of POEMS syndrome after treatments...
February 2018: Neuro-ophthalmology
Claudia Müller, Carol Charniga, Sally Temple, Silvia C Finnemann
With stem cell-derived retinal pigment epithelial (RPE) replacement therapies in clinical testing, establishing potency of RPE prior to transplantation is imperative. Phagocytosis of photoreceptor outer segment fragments (POS) is a key indicator of RPE functionality. Comparing RPE derived from different donor human adult RPE stem cell lines, we found that cells were either high-phagocytic or low-phagocytic despite sharing phagocytic receptors and ligands, junctional ZO-1, and lack of epithelial-mesenchymal transition...
February 9, 2018: Stem Cell Reports
Caroline Brandl, Bernhard H F Weber
Today, the search for therapeutic options to treat retinal degeneration often relies on an in-depth understanding of the underlying pathological events. Alternatively, it is conceivable to search, in an undirected screening approach, for chemical compounds affecting disease outcome. For both approaches, there is an urgent need for in vitro and, ideally, in vivo disease models that adequately reflect the site of pathology. Currently available animal models possess limitations as they often develop only defined aspects of disease...
February 16, 2018: Klinische Monatsblätter Für Augenheilkunde
Reena Rathod, Harshini Surendran, Rajani Battu, Jogin Desai, Rajarshi Pal
Retinal degenerative disorders are a leading cause of the inherited, irreversible and incurable vision loss. While various rodent model systems have provided crucial information in this direction.lack of disease-relevant tissue availability and species-specific differences have proven to be a major roadblock. Human induced pluripotent stem cells (iPSC) have opened up a whole new avenue of possibilities not just in understanding the disease mechanism but also potential therapeutic approaches towards a cure. In this review, we have summarized recent advances in the methods of deriving retinal cell types from iPSCs which can serve as a renewable source of disease-relevant cell population for basic as well as translational studies...
February 12, 2018: Journal of Chemical Neuroanatomy
Sandra Petrus-Reurer, Hammurabi Bartuma, Monica Aronsson, Sofie Westman, Fredrik Lanner, Anders Kvanta
Geographic atrophy (GA), the late stage of dry age-related macular degeneration is characterized by loss of the retinal pigment epithelial (RPE) layer, which leads to subsequent degeneration of vital retinal structures (e.g., photoreceptors) causing severe vision impairment. Similarly, RPE-loss and decrease in visual acuity is seen in long-term follow up of patients with advanced wet age-related macular degeneration (AMD) receiving intravitreal anti-vascular endothelial growth factor (VEGF) treatment. Therefore, on the one hand, it is fundamental to efficiently derive RPE cells from an unlimited source that could serve as replacement therapy...
January 22, 2018: Journal of Visualized Experiments: JoVE
Svenja Pachernegg, Sebastian Eilebrecht, Elke Eilebrecht, Hendrik Schöneborn, Sebastian Neumann, Arndt G Benecke, Michael Hollmann
For years, GluN3A was solely considered to be a dominant-negative modulator of NMDARs, since its incorporation into receptors alters hallmark features of conventional NMDARs composed of GluN1/GluN2 subunits. Only recently, increasing evidence has accumulated that GluN3A plays a more diversified role. It is considered to be critically involved in the maturation of glutamatergic synapses, and it might act as a molecular brake to prevent premature synaptic strengthening. Its expression pattern supports a putative role during neural development, since GluN3A is predominantly expressed in early pre- and postnatal stages...
2018: PloS One
Seoh Wei Teh, Pooi Ling Mok, Munirah Abd Rashid, Mae-Lynn Catherine Bastion, Normala Ibrahim, Akon Higuchi, Kadarkarai Murugan, Rajan Mariappan, Suresh Kumar Subbiah
Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area...
February 13, 2018: International Journal of Molecular Sciences
Maciej Daniszewski, Anne Senabouth, Quan H Nguyen, Duncan E Crombie, Samuel W Lukowski, Tejal Kulkarni, Valentin M Sluch, Jafar S Jabbari, Xitiz Chamling, Donald J Zack, Alice Pébay, Joseph E Powell, Alex W Hewitt
We used single cell sequencing technology to characterize the transcriptomes of 1,174 human embryonic stem cell-derived retinal ganglion cells (RGCs) at the single cell level. The human embryonic stem cell line BRN3B-mCherry (A81-H7), was differentiated to RGCs using a guided differentiation approach. Cells were harvested at day 36 and prepared for single cell RNA sequencing. Our data indicates the presence of three distinct subpopulations of cells, with various degrees of maturity. One cluster of 288 cells showed increased expression of genes involved in axon guidance together with semaphorin interactions, cell-extracellular matrix interactions and ECM proteoglycans, suggestive of a more mature RGC phenotype...
February 13, 2018: Scientific Data
Jing Zhou, Alberto Benito-Martin, Jason Mighty, Lynne Chang, Shima Ghoroghi, Hao Wu, Madeline Wong, Sara Guariglia, Petr Baranov, Michael Young, Rajendra Gharbaran, Mark Emerson, Milica Tesic Mark, Henrik Molina, M Valeria Canto-Solar, Hector Peinado Selgas, Stephen Redenti
A range of cell types, including embryonic stem cells, neurons and astrocytes have been shown to release extracellular vesicles (EVs) containing molecular cargo. Across cell types, EVs facilitate transfer of mRNA, microRNA and proteins between cells. Here we describe the release kinetics and content of EVs from mouse retinal progenitor cells (mRPCs). Interestingly, mRPC derived EVs contain mRNA, miRNA and proteins associated with multipotency and retinal development. Transcripts enclosed in mRPC EVs, include the transcription factors Pax6, Hes1, and Sox2, a mitotic chromosome stabilizer Ki67, and the neural intermediate filaments Nestin and GFAP...
February 12, 2018: Scientific Reports
Ye He, Hai-Bo Li, Xin Li, Yi Zhou, Xiao-Bo Xia, Wei-Tao Song
BACKGROUND/AIMS: Retinal Müller cells could be induced to differentiate into retinal ganglion cells (RGCs), but RGCs derived from Müller cells have defects in axon growth, leading to a defect in signal conduction. In this study we aimed to explore the role of miR-124 in axon growth of RGCs derived from Müller cells. METHODS: Müller cells were isolated from rat retina and induced to dedifferentiate into retinal stem cells. The stem cells were infected by PGC-FU-Atoh7-GFP lentivirus and then transfected with miR-124 or anti-miR-124, and the length of axon was compared...
February 5, 2018: Cellular Physiology and Biochemistry
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