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Retina, stem cells

Min Yu, Sanja Bojic, Gustavo S Figueiredo, Paul Rooney, Julian de Havilland, Anne Dickinson, Francisco C Figueiredo, Majlinda Lako
The cornea is a self-renewing tissue located at the front of the eye. Its transparency is essential for allowing light to focus onto the retina for visual perception. The continuous renewal of corneal epithelium is supported by limbal stem cells (LSCs) which are located in the border region between conjunctiva and cornea known as the limbus. Ex vivo expansion of LSCs has been successfully applied in the last two decades to treat patients with limbal stem cell deficiency (LSCD). Various methods have been used for their expansion, yet the most widely used culture media contains a number of ingredients derived from animal sources which may compromise the safety profile of human LSC transplantation...
September 28, 2016: Experimental Eye Research
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
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
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
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
Cassie A Ludwig, Theodore Leng
The authors report two cases of posterior retinotomy closure following subretinal stem cell transplantation for age-related macular degeneration with a 30-gauge needle - a larger bore needle than those used in prior studies. Partial retinotomy closure was seen on optical coherence tomography within 24 hours in one patient, whereas complete closure occurred by the 5-month and 1-year follow-up visits. A trace retinal hemorrhage occurred in one case, with resolution by 12 weeks. These findings demonstrate the likelihood of uncomplicated, spontaneous retinotomy closure following subretinal stem cell transplantation with a 30-gauge needle...
September 1, 2016: Ophthalmic Surgery, Lasers & Imaging Retina
Benjamin Bakondi, Sergey Girman, Bin Lu, Shaomei Wang
: : We previously demonstrated that subretinal injection (SRI) of isogenic mesenchymal stem cells (MSCs) reduced the severity of retinal degeneration in Royal College of Surgeons rats in a focal manner. In contrast, intravenous MSC infusion (MSC(IV)) produced panoptic retinal rescue. By combining these treatments, we now show that MSC(IV) supplementation potentiates the MSC(SRI)-mediated rescue of photoreceptors and visual function. Electrophysiological recording from superior colliculi revealed 3...
September 9, 2016: Stem Cells Translational Medicine
Narges Aghaallaei, Franziska Gruhl, Colin Q Schaefer, Tobias Wernet, Venera Weinhardt, Lázaro Centanin, Felix Loosli, Tilo Baumbach, Joachim Wittbrodt
Recently, a stochastic model of symmetrical stem cell division followed by neutral drift has been proposed for intestinal stem cells (ISCs), which has been suggested to represent the predominant mode of stem cell progression in mammals. In contrast, stem cells in the retina of teleost fish show an asymmetric division mode. To address whether the mode of stem cell division follows phylogenetic or ontogenetic routes, we analysed the entire gastrointestinal tract of the teleost medaka (Oryzias latipes). X-ray microcomputed tomography shows a correlation of 3D topography with the functional domains...
October 1, 2016: Development
Paul W Hamilton, Jonathan J Henry
The frog, Xenopus laevis, is capable of completely regenerating a lens from the cornea epithelium. Because this ability appears to be limited to the larval stages of Xenopus, virtually all the work to understand the mechanisms regulating this process has been limited to pre-metamorphic tadpoles. It has been reported that the post-metamorphic cornea is competent to regenerate under experimental conditions, despite the fact that the in vivo capacity to regenerate is lost; however, that work didn't examine the regenerative potential of different regions of the cornea...
August 26, 2016: Experimental Eye Research
Elad Moisseiev, Zeljka Smit-McBride, Sharon Oltjen, Pengfei Zhang, Robert J Zawadzki, Monica Motta, Christopher J Murphy, Whitney Cary, Geralyn Annett, Jan A Nolta, Susanna S Park
PURPOSE: Intravitreal murine lineage-negative bone marrow (BM) hematopoietic cells slow down retinal degeneration. Because human BM CD34+ hematopoietic cells are not precisely comparable to murine cells, this study examined the effect of intravitreal human BM CD34+ cells on the degenerating retina using a murine model. METHODS: C3H/HeJrd1/rd1 mice, immunosuppressed systemically with tacrolimus and rapamycin, were injected intravitreally with PBS (n = 16) or CD34+ cells (n = 16) isolated from human BM using a magnetic cell sorter and labeled with enhanced green fluorescent protein (EGFP)...
August 1, 2016: Investigative Ophthalmology & Visual Science
Zhen-Kai Wu, Lan Cao, Xue-Yong Zhang, Wei-Tao Song, Xiao-Bo Xia
AIM: To investigate the role of Brn-3b in differentiation process of stem cells derived from retinal Müller cells into the ganglion cell. METHODS: The passage culture method of Müller cells from retina of newborn Sprague Dawley rats was carried out by repeated incomplete pancreatic enzyme digestion method. The cells were detected by fluorescence-activated cell sorter (FACS), immunohistochemistry technology and reverse transcription-polymerase chain reaction (RT-PCR) to determine the purity...
2016: International Journal of Ophthalmology
Jordi Monés, Marta Leiva, Teresa Peña, Gema Martínez, Marc Biarnés, Miriam Garcia, Anna Serrano, Eduardo Fernandez
PURPOSE: To establish the dose of subretinal sodium iodate (NaIO3) in order to create a toxin-induced large animal model of selective circumscribed atrophy of outer retinal layers, the retinal pigment epithelium (RPE), and photoreceptors, by spectral-domain optical coherence tomography (SD-OCT) and immunocytochemistry. METHODS: Fifteen male and female healthy Yorkshire pigs received unilateral subretinal escalating doses of NaIO3 under general anesthesia. In all the animals, volumes of 0...
August 1, 2016: Investigative Ophthalmology & Visual Science
I P Seitz, K Achberger, S Liebau, M D Fischer
In ophthalmology, regenerative medicine is rapidly becoming a reality. Cell based treatment strategies in end stage retinal degeneration may be of therapeutic value, whatever the mechanism of disease mechanism. However, while corneal transplantation is commonly performed with excellent results, many obstacles must be overcome before retinal transplants can become clinically useful. The major problems are the production of appropriate transplants and functional integration in situ. New technologies allow the production of autologous transplants by inducing pluripotency in adult somatic cells...
August 1, 2016: Klinische Monatsblätter Für Augenheilkunde
Bikun Xian, Yichi Zhang, Yuting Peng, Jianfa Huang, Weihua Li, Wencong Wang, Min Zhang, Kaijing Li, Hening Zhang, Minglei Zhao, Xing Liu, Bing Huang
: : Adult human peripheral blood mononuclear cells (hPBMCs) exhibit pluripotency in vitro and so may be a valuable cell source for regenerative therapies. The efficacy of such therapies depends on the survival, differentiation, migration, and integration capacity of hPBMCs in specific tissues. In this study, we examined these capacities of transplanted hPBMCs in mouse retina as well functional improvement after transplant. We isolated hPBMCs and preinduced them for 4 days in media preconditioned with postnatal day 1 rat retina explants...
July 25, 2016: Stem Cells Translational Medicine
Lixiong Gao, Xi Chen, Yuxiao Zeng, Qiyou Li, Ting Zou, Siyu Chen, Qian Wu, Caiyun Fu, Haiwei Xu, Zheng Qin Yin
The vertebrate retina is a highly multilayered nervous tissue with a large diversity of cellular components. With the development of stem cell technologies, human retinas can be generated in three-dimensional (3-D) culture in vitro. However, understanding the factors modulating key productive processes and the way that they influence development are far from clear. Oxygen, as the most essential element participating in metabolism, is a critical factor regulating organic development. In this study, using 3-D culture of human stem cells, we examined the effect of intermittent high oxygen treatment (40% O2) on the formation and cellular behavior of neural retinas (NR) in the embryonic body (EB)...
2016: Scientific Reports
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