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Retinal stem cells

Andrea Moretti, Jianfeng Li, Stefano Donini, Robert W Sobol, Menico Rizzi, Silvia Garavaglia
The aldehyde dehydrogenase family 1 member A3 (ALDH1A3) catalyzes the oxidation of retinal to the pleiotropic factor retinoic acid using NAD(+). The level of ALDHs enzymatic activity has been used as a cancer stem cell marker and seems to correlate with tumour aggressiveness. Elevated ALDH1A3 expression in mesenchymal glioma stem cells highlights the potential of this isozyme as a prognosis marker and drug target. Here we report the first crystal structure of human ALDH1A3 complexed with NAD(+) and the product all-trans retinoic acid (REA)...
October 19, 2016: Scientific Reports
Eren Çerman, Tolga Akkoç, Muhsin Eraslan, Özlem Şahin, Selvinaz Özkara, Fugen Vardar Aker, Cansu Subaşı, Erdal Karaöz, Tunç Akkoç
[This corrects the article DOI: 10.1371/journal.pone.0156495.].
2016: PloS One
Whitney A Greene, Teresa A Burke, Elaine D Por, Ramesh R Kaini, Heuy-Ching Wang
Purpose: The purpose of this study was to characterize the secretion profile of induced pluripotent stem cell-derived retinal pigment epithelium (iPS-RPE) during wound healing. iPS-RPE was used to develop an in vitro wound healing model. We hypothesized that iPS-RPE secretes cytokines and growth factors which act in an autocrine manner to promote migration and proliferation of cells during wound healing. Methods: iPS-RPE was grown in transwells until fully confluent and pigmented...
August 1, 2016: Investigative Ophthalmology & Visual Science
Ji-Eun Im, Sun-Hwa Song, Wonhee Suh
PURPOSE: Stem cell factor (SCF) has been recently acknowledged as a novel endothelial permeability factor. However, the mechanisms by which SCF-induced activation of the SCF cognate receptor, cKit, enhances endothelial permeability have not been fully elucidated. This study aimed to investigate the role of Src in SCF-induced breakdown of the blood-retinal barrier (BRB). METHODS: In vitro endothelial permeability and in vivo retinal vascular permeability assays were performed to investigate the role of Src in SCF-induced breakdown of the BRB...
2016: Molecular Vision
Marissa B Larochelle, Ryan Phan, John Craddock, Mark J Abzug, Donna Curtis, Christine C Robinson, Roger H Giller, Shaun Cosgrove, Frank Siringo, Emily McCourt, Alan G Palestine
PURPOSE: The incidence of cytomegalovirus (CMV) retinitis in the pediatric allogeneic hematopoietic stem cell transplant (HSCT) population is unknown. We report a cluster of 5 pediatric patients with CMV retinitis diagnosed in a 12-month period, and compare this to the rate of CMV viremia and retinitis in the four years prior. Presented is the ophthalmic screening protocol developed in response to this experience. DESIGN: Retrospective cross-sectional study. METHODS: A retrospective chart review was performed on patients at Children's Hospital of Colorado (CHCO) who received allogeneic HSCT between January 2010 and December 2014...
October 13, 2016: American Journal of Ophthalmology
Pooja Teotia, Divyan A Chopra, Shashank Manohar Dravid, Matthew J Van Hook, Fang Qiu, John Morrison, Angie Rizzino, Iqbal Ahmad
Glaucoma is a complex group of diseases wherein a selective degeneration of retinal ganglion cells (RGCs) leads to irreversible loss of vision. A comprehensive approach to glaucomatous RGC degeneration may include stem cells to functionally replace dead neurons through transplantation and understand RGCs vulnerability using a disease in a dish stem cell model. Both approaches require the directed generation of stable, functional, and target-specific RGCs from renewable sources of cells, i.e., the embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)...
October 6, 2016: Stem Cells
Christopher J Sifuentes, Jung-Woong Kim, Anand Swaroop, Pamela A Raymond
Purpose: Zebrafish neurons regenerate from Müller glia following retinal lesions. Genes and signaling pathways important for retinal regeneration in zebrafish have been described, but our understanding of how Müller glial stem cell properties are regulated is incomplete. Mammalian Müller glia possess a latent neurogenic capacity that might be enhanced in regenerative therapies to treat degenerative retinal diseases. Methods: To identify transcriptional changes associated with stem cell properties in zebrafish Müller glia, we performed a comparative transcriptome analysis from isolated cells at 8 and 16 hours following an acute photic lesion, prior to the asymmetric division that produces retinal progenitors...
October 1, 2016: Investigative Ophthalmology & Visual Science
Lisa E Kelly, Reyna I Martinez-De Luna, Heithem M El-Hodiri
The Retinal homeobox (rax) gene is expressed in vertebrate retinal progenitor and stem cells and is essential for retinal development. In frogs, rax is expressed in the ciliary marginal zone (CMZ), a region containing retinal progenitor and stem cells at the anterior of the eye. Little is known regarding regulation of rax transcription and regulation of transcription of rax targets. We found that three ultra-conserved genomic elements (UCEs) flanking the rax coding region regulate expression of a rax promoter-GFP transgene in Xenopus tadpoles...
October 3, 2016: Genesis: the Journal of Genetics and Development
Bo Yu, Hui Shao, Chang Su, Yuanfeng Jiang, Xiteng Chen, Lingling Bai, Yan Zhang, Qiutang Li, Xiaomin Zhang, Xiaorong Li
Although accumulated evidence supports the notion that mesenchymal stem cells (MSCs) act in a paracrine manner, the mechanisms are still not fully understood. Recently, MSC-derived exosomes (MSC-Exos), a type of microvesicle released from MSCs, were thought to carry functional proteins and RNAs to recipient cells and play therapeutic roles. In the present study, we intravitreally injected MSCs derived from either mouse adipose tissue or human umbilical cord, and their exosomes to observe and compare their functions in a mouse model of laser-induced retinal injury...
September 30, 2016: Scientific Reports
Holly Yu Chen, Koray Dogan Kaya, Lijin Dong, Anand Swaroop
PURPOSE: The generation of three-dimensional (3D) organoids with optic cup-like structures from pluripotent stem cells has created opportunities for investigating mammalian retinal development in vitro. However, retinal organoids in culture do not completely reflect the developmental state and in vivo architecture of the rod-dominant mouse retina. The goals of this study were to develop an efficient protocol for generating retinal organoids from stem cells and examine the morphogenesis of rods in vitro...
2016: Molecular Vision
Robert E MacLaren, Jean Bennett, Steven D Schwartz
Gene and cell therapies have the potential to prevent, halt, or reverse diseases of the retina in patients with currently incurable blinding conditions. Over the past 2 decades, major advances in our understanding of the pathobiologic basis of retinal diseases, coupled with growth of gene transfer and cell transplantation biotechnologies, have created optimism that previously blinding retinal conditions may be treatable. It is now possible to deliver cloned genes safely and stably to specific retinal cell types in humans...
October 2016: Ophthalmology
Thibaud Mathis, Michael Housset, Chiara Eandi, Fanny Beguier, Sara Touhami, Sacha Reichman, Sebastien Augustin, Pauline Gondouin, José-Alain Sahel, Laurent Kodjikian, Olivier Goureau, Xavier Guillonneau, Florian Sennlaub
Orthodenticle homeobox 2 (OTX2) controls essential, homeostatic retinal pigment epithelial (RPE) genes in the adult. Using cocultures of human CD14(+) blood monocytes (Mos) and primary porcine RPE cells and a fully humanized system using human-induced pluripotent stem cell-derived RPE cells, we show that activated Mos markedly inhibit RPEOTX2 expression and resist elimination in contact with the immunosuppressive RPE. Mechanistically, we demonstrate that TNF-α, secreted from activated Mos, mediates the downregulation of OTX2 and essential RPE genes of the visual cycle among others...
September 22, 2016: Aging Cell
Yuriko Minegishi, XunLun Sheng, Kazutoshi Yoshitake, Yuri Sergeev, Daisuke Iejima, Yoshio Shibagaki, Norikazu Monma, Kazuho Ikeo, Masaaki Furuno, Wenjun Zhuang, Yani Liu, Weining Rong, Seisuke Hattori, Takeshi Iwata
Leber congenital amaurosis (LCA) is a hereditary early-onset retinal dystrophy that is accompanied by severe macular degeneration. In this study, novel compound heterozygous mutations were identified as LCA-causative in chaperonin-containing TCP-1, subunit 2 (CCT2), a gene that encodes the molecular chaperone protein, CCTβ. The zebrafish mutants of CCTβ are known to exhibit the eye phenotype while its mutation and association with human disease have been unknown. The CCT proteins (CCT α-θ) forms ring complex for its chaperon function...
2016: Scientific Reports
Junhua Wang, Peter D Westenskow, Mingliang Fang, Martin Friedlander, Gary Siuzdak
Photoreceptor degeneration is characteristic of vision-threatening diseases including age-related macular degeneration. Photoreceptors are metabolically demanding cells in the retina, but specific details about their metabolic behaviours are unresolved. The quantitative metabolomics of retinal degeneration could provide valuable insights and inform future therapies. Here, we determined the metabolomic 'fingerprint' of healthy and dystrophic retinas in rat models using optimized metabolite extraction techniques...
October 28, 2016: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
Srilatha Jasty, Subramanian Krishnakumar
Millions of people around the world suffer from retinal degenerative diseases at varying degrees of vision loss including, complete blindness that are caused by the damage to cells of the retina. The cell replacement therapy could be a promising tool in treating these conditions, since the stem/progenitor cells could be isolated form adult ciliary pigment epithelial cells and could be differentiated into retinal phenotypes in vitro and could be of great importance. The present study aims to identify the role of epigenetic regulators during cellular differentiation, which involves loss of pluripotency and gain of lineage and cell type-specific characteristics...
September 15, 2016: Brain Research
Sunao Sugita, Yuko Iwasaki, Kenichi Makabe, Hiroyuki Kamao, Michiko Mandai, Takashi Shiina, Kazumasa Ogasawara, Yasuhiko Hirami, Yasuo Kurimoto, Masayo Takahashi
There is an ongoing controversy as to whether major histocompatibility complex (MHC) matching is a solution for allogeneic stem cell transplantation. In the present study, we established retinal pigment epithelial (RPE) cells from induced pluripotent stem cells (iPSCs) in MHC homozygote donors. We observed no rejection signs in iPSC-derived RPE allografts of MHC-matched animal models without immunosuppression, whereas there were immune attacks around the graft and retinal tissue damage in MHC-mismatched models...
October 11, 2016: Stem Cell Reports
Sunao Sugita, Yuko Iwasaki, Kenichi Makabe, Takafumi Kimura, Takaomi Futagami, Shinji Suegami, Masayo Takahashi
Allografts of retinal pigment epithelial (RPE) cells have been considered for the treatment of ocular diseases. We recently started the transplantation of induced pluripotent stem cell (iPSC)-derived RPE cells for patients with age-related macular degeneration (autogenic grafts). However, there are at least two problems with this approach: (1) high cost, and (2) uselessness for acute patients. To resolve these issues, we established RPE cells from induced iPSCs in HLA homozygote donors. In vitro, human T cells directly recognized allogeneic iPSC-derived RPE cells that expressed HLA class I/II antigens...
October 11, 2016: Stem Cell Reports
Christopher J Tracy, Rebecca E H Whiting, Jacqueline W Pearce, Baye G Williamson, Daniella P Vansteenkiste, Lauren E Gillespie, Leilani J Castaner, Jeffrey N Bryan, Joan R Coates, Cheryl A Jensen, Martin L Katz
The CLN2 form of neuronal ceroid lipofuscinosis is a neurodegenerative disease that results from mutations in the TPP1 gene. Affected children exhibit progressive declines in most neurological functions including vision. Functional declines are accompanied by progressive brain and retinal atrophy. TPP1 encodes the soluble lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Dachshunds with a TPP1 null mutation exhibit a disorder very similar to human CLN2 disease. Periodic infusion of recombinant TPP1 protein or a single injection of a TPP1 gene therapy vector into the cerebrospinal fluid of affected dogs significantly delays the onset and progression of neurological signs but does not slow vision loss or retinal degeneration...
September 13, 2016: Experimental Eye Research
Justo Aznar, Julio Tudela
BACKGROUND: The use of stem cells in regenerative medicine has major therapeutic potential. Recent clinical trials using cells derived from human stem cells are showing encouraging results, although these should be assessed with the necessary caution. DISCUSSION: Some media have reported the results of these trials without due care, perhaps creating expectations that do not match the reality of the facts. This paper describes some of the recent advances in the use of human stem cells, particularly those made in the area of ophthalmology, and more specifically, in Stargardt's disease and age-related macular degeneration (AMD)...
May 2016: Cuadernos de Bioética: Revista Oficial de la Asociación Española de Bioética y Ética Médica
Yuiko Hasegawa, Nozomu Takata, Satoru Okuda, Masako Kawada, Mototsugu Eiraku, Yoshiki Sasai
We previously demonstrated that mouse embryonic stem cell (mESC)-derived retinal epithelium self-forms an optic cup-like structure. In the developing retina, the dorsal and ventral sides differ in terms of local gene expression and morphological features. This aspect has not yet been shown in vitro Here we demonstrate that mESC-derived retinal tissue spontaneously acquires polarity reminiscent of the dorsal-ventral (D-V) patterning of the embryonic retina. Tbx5 and Vax2 were expressed in a mutually exclusive manner, as seen in vivo Three-dimensional morphometric analysis showed that the in vitro-formed optic cup often contains cleft structures resembling the embryonic optic fissure...
September 15, 2016: Development
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