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Retina, transplantation

Phoebe Lin
PURPOSE OF REVIEW: The intestinal commensal microbiota are important in shaping immune cell repertoire and are influenced by host genetics. Because of this intricate interaction, an intestinal dysbiosis has been associated with multiple immune-mediated polygenic diseases. This review summarizes the literature on how alterations in the intestinal microbiota contribute to immune-mediated ocular disease, and how to potentially target the gut microbiome for therapeutic benefit. RECENT FINDINGS: Several groups have demonstrated the importance of the intestinal microbiome in uveitis pathogenesis...
March 13, 2018: Current Opinion in Ophthalmology
Gaia Gestri, Naiara Bazin-Lopez, Clarissa Scholes, Stephen W Wilson
Coloboma is a defect in the morphogenesis of the eye that is a consequence of failure of choroid fissure fusion. It is among the most common congenital defects in humans and can significantly impact vision. However, very little is known about the cellular mechanisms that regulate choroid fissure closure. Using high-resolution confocal imaging of the zebrafish optic cup, we find that apico-basal polarity is re-modeled in cells lining the fissure in proximal to distal and inner to outer gradients during fusion...
2018: Frontiers in Cellular Neuroscience
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
Andrea Lavazza, Marcello Massimini
Organoids are three-dimensional biological structures grown in vitro from different kinds of stem cells that self-organise mimicking real organs with organ-specific cell types. Recently, researchers have managed to produce human organoids which have structural and functional properties very similar to those of different organs, such as the retina, the intestines, the kidneys, the pancreas, the liver and the inner ear. Organoids are considered a great resource for biomedical research, as they allow for a detailed study of the development and pathologies of human cells; they also make it possible to test new molecules on human tissue...
February 28, 2018: Journal of Medical Ethics
Sehwon Koh, William J Chen, Nadine S Dejneka, Ian R Harris, Bin Lu, Sergey Girman, Joshua Saylor, Shaomei Wang, Cagla Eroglu
Human umbilical tissue-derived cells (hUTC or palucorcel) are currently under clinical investigation for the treatment of geographic atrophy, a late stage of macular degeneration, but how hUTC transplantation mediates vision recovery is not fully elucidated. Subretinal administration of hUTC preserves visual function in the Royal College of Surgeons (RCS) rat, a genetic model of retinal degeneration caused by Mertk loss-of-function. hUTC secrete synaptogenic and neurotrophic factors that improve the health and connectivity of the neural retina...
February 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Wataru Kobayashi, Akishi Onishi, Hung-Ya Tu, Yuji Takihara, Michiru Matsumura, Kazuko Tsujimoto, Masaru Inatani, Toru Nakazawa, Masayo Takahashi
Purpose: We aimed to establish purification and culture systems for retinal ganglion cells (RGCs) differentiated from mouse and human pluripotent stem cells (PSC) for in vitro and regenerative medicine studies. Methods: We used a two-step immunopanning method to purify RGCs from mouse and human PSC-derived three-dimensional (3D) retinal organoids. To assess the method, we purified RGCs from 3D retinal organoids derived from embryonic stem cells (ESCs) generated from Thy1-EGFP transgenic (TG) mice...
February 1, 2018: Investigative Ophthalmology & Visual Science
Mingyue Luo, Youxin Chen
As a constituent of blood-retinal barrier and retinal outer segment (ROS) scavenger, retinal pigmented epithelium (RPE) is fundamental to normal function of retina. Malfunctioning of RPE contributes to the onset and advance of retinal degenerative diseases. Up to date, RPE replacement therapy is the only possible method to completely reverse retinal degeneration. Transplantation of human RPE stem cell-derived RPE (hRPESC-RPE) has shown some good results in animal models. With promising results in terms of safety and visual improvement, human embryonic stem cell-derived RPE (hESC-RPE) can be expected in clinical settings in the near future...
2018: International Journal of Ophthalmology
Ankush Thakur, Shawn Mishra, Juan Pena, Jing Zhou, Stephen Redenti, Robert Majeska, Maribel Vazquez
Strategies to replace retinal photoreceptors lost to damage or disease rely upon the migration of replacement cells transplanted into sub-retinal spaces. A significant obstacle to the advancement of cell transplantation for retinal repair is the limited migration of transplanted cells into host retina. In this work, we examine the adhesion and displacement responses of retinal progenitor cells on extracellular matrix substrates found in retina as well as widely used in the design and preparation of transplantable scaffolds...
January 2018: Journal of Tissue Engineering
Michael F Marmor
PURPOSE: To analyze an unusual case of widespread chorioretinopathy after cardiac transplantation for its potential etiology and clinical significance. METHODS: Clinical examinations included widefield and macular color and fundus autofluorescence photography, spectral domain optical coherence tomography, fluorescein angiography and indocyanine green angiography, full-field electroretinography, and Goldmann visual fields. PATIENT: A 44-year-old Hispanic woman was referred to rule out retinitis pigmentosa...
January 16, 2018: Retinal Cases & Brief Reports
Paul V Waldron, Fabiana Di Marco, Kamil Kruczek, Joana Ribeiro, Anna B Graca, Claire Hippert, Nozie D Aghaizu, Aikaterini A Kalargyrou, Amanda C Barber, Giulia Grimaldi, Yanai Duran, Samuel J I Blackford, Magdalena Kloc, Debbie Goh, Eduardo Zabala Aldunate, Robert D Sampson, James W B Bainbridge, Alexander J Smith, Anai Gonzalez-Cordero, Jane C Sowden, Robin R Ali, Rachael A Pearson
Human vision relies heavily upon cone photoreceptors, and their loss results in permanent visual impairment. Transplantation of healthy photoreceptors can restore visual function in models of inherited blindness, a process previously understood to arise by donor cell integration within the host retina. However, we and others recently demonstrated that donor rod photoreceptors engage in material transfer with host photoreceptors, leading to the host cells acquiring proteins otherwise expressed only by donor cells...
January 4, 2018: Stem Cell Reports
Yuyao Wang, Dandan Zhang, Bingqiao Shen, Yi Zhang, Ping Gu
Visual impairment caused by retinal degeneration is primarily attributed to the irreversible degradation of retinal neurons or the adjacent retinal pigment epithelium (RPE). No efficient clinical therapies to restore or improve visual ability are currently available. Cell therapy has been touted as a promising strategy to overcome this challenge. Progenitor/stem cells may be obtained from both ocular and non-ocular tissues. The former mainly includes retinal progenitor cells (RPCs), whereas the latter comprises embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which have been utilized in stem cell replacement therapy studies ranging from proof-of-concept animal models to clinical trials in humans...
December 27, 2017: Current Stem Cell Research & Therapy
Li Huang, Zongyi Li, Haibin Tian, Weiguo Wang, Dawei Cui, Zhe Zhou, Xiao Chen, Herman S Cheung, Guo-Tong Xu, Yu Chen
BACKGROUND: Retinal degeneration (RD) is a leading cause of irreversible blindness, affecting millions of people worldwide. Stem cell transplantation has been considered a promising therapy for retinal degenerative diseases. This study aimed to investigate the therapeutic potential of human periodontal ligament-derived stem cells (hPDLSCs) for intervention in the progress of this degeneration in the Royal College Surgeons (RCS) rat. METHODS: hPDLSCs were injected into the subretinal space of 3-week-old RCS rats...
December 22, 2017: Stem Cell Research & Therapy
Laura Garcia-Garcia, Sergio Recalde, Maria Hernandez, Jaione Bezunartea, Juan Roberto Rodriguez-Madoz, Sandra Johnen, Sabine Diarra, Corinne Marie, Zsuzsanna Izsvák, Zoltán Ivics, Daniel Scherman, Martina Kropp, Gabriele Thumann, Felipe Prosper, Patricia Fernandez-Robredo, Alfredo Garcia-Layana
Pigment epithelium derived factor (PEDF) is a potent antiangiogenic, neurotrophic, and neuroprotective molecule that is the endogenous inhibitor of vascular endothelial growth factor (VEGF) in the retina. An ex vivo gene therapy approach based on transgenic overexpression of PEDF in the eye is assumed to rebalance the angiogenic-antiangiogenic milieu of the retina, resulting in growth regression of choroidal blood vessels, the hallmark of neovascular age-related macular degeneration. Here, we show that rat pigment epithelial cells can be efficiently transfected with the PEDF-expressing non-viral hyperactive Sleeping Beauty transposon system delivered in a form free of antibiotic resistance marker miniplasmids...
December 15, 2017: Molecular Therapy. Nucleic Acids
Jarel K Gandhi, Zahid Manzar, Lori A Bachman, Cynthia Andrews-Pfannkoch, Travis Knudsen, Matthew Hill, Hannah Schmidt, Raymond Iezzi, Jose S Pulido, Alan D Marmorstein
Recent phase 1 trials of embryonic stem cell and induced pluripotent stem cell (iPSCs) derived RPE transplants for the treatment of macular degeneration have demonstrated the relative safety of this process. However, there is concern over clumping, thickening, folding, and wrinkling of the transplanted RPE. To deliver a flat RPE monolayer, current phase 1 trials are testing synthetic substrates for RPE transplantation. These substrates, however, cause localized inflammation and fibrosis in animal models due to long degradation times...
December 9, 2017: Acta Biomaterialia
Taty Anna Kamarudin, Sanja Bojic, Joseph Collin, Min Yu, Sameer Alharthi, Harley Buck, Alex Shortt, Lyle Armstrong, Francisco C Figueiredo, Majlinda Lako
Cornea is a clear outermost layer of the eye which enables transmission of light onto the retina. The transparent corneal epithelium is regenerated by limbal stem cells (LSCs), whose loss/dysfunction results in LSCs deficiency (LSCD). Ex vivo expansion of autologous LSCs obtained from patient's healthy eye followed by transplantation onto the LSCs damaged/deficient eye, has provided a successful treatment for unilateral LSCD. However, this is not applicable to patient with total bilateral LSCD, where LSCs are lost/damaged from both eyes...
March 2018: Stem Cells
Barbara Parolini, Dilraj S Grewal, Sajish J Pinackatt, Andrea Baldi, Attilio Di Salvatore, Gianluca Besozzi, Alessandro Finzi, Daniele Cardillo, Tamer H Mahmoud
PURPOSE: To evaluate the feasibility and initial functional and anatomical outcomes of transplanting a full-thickness free graft of choroid and retinal pigment epithelium (RPE), along with neurosensory retina in advanced fibrosis and atrophy associated with end-stage exudative age-related macular degeneration with and without a concurrent refractory macular hole. METHODS: During vitrectomy, an RPE-choroidal and neurosensory retinal free graft was harvested in nine eyes of nine patients...
November 23, 2017: Retina
L Wang, P Li, Y Tian, Z Li, C Lian, Q Ou, C Jin, F Gao, J-Y Xu, J Wang, F Wang, J Zhang, J Zhang, W Li, H Tian, L Lu, G-T Xu
BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential candidates for treating retinal degeneration (RD). OBJECTIVE: To further study the biology and therapeutic effects of the hUC-MSCs on retinal degeneration. METHODS: Two hUC-MSC subpopulations, termed hUC-MSC1 and hUC-MSC2, were isolated by single-cell cloning method and their therapeutic functions were compared in RCS rat, a RD model. RESULTS: Although both subsets satisfied the basic requirements for hUC-MSCs, they were significantly different in morphology, proliferation rate, differentiation capacity, phenotype and gene expression...
2017: Current Molecular Medicine
Langyue Xue, Yuxiao Zeng, Qiyou Li, Yijian Li, Zhengya Li, Haiwei Xu, Zhengqin Yin
There is still not an effective treatment for continuous retinal light exposure and subsequent photoreceptor degeneration. Olfactory ensheathing cell (OEC) transplantation has been shown to be neuroprotective in spinal cord, and optic nerve injury and retinitis pigmentosa. However, whether OECs protect rat photoreceptors against light-induced damage and how this may work is unclear. Thus, to elucidate this mechanism, purified rat OECs were grafted into the subretinal space of a Long-Evans rat model with light-induced photoreceptor damage...
November 3, 2017: Oncotarget
I P Khoroshilova-Maslova, N L Leparskaya, E A Vorotelyak, A V Vasiliev
AIM: to investigate the role of heterogeneous fibroblasts in the development of epiretinal membrane in eyes with modeled proliferative vitreoretinopathy. MATERIAL AND METHODS: The material for investigation were 6 eyes of 3 Chinchilla rabbits. Suspended fibroblasts (fibroblasts of the human skin - 200000 cells in 0.1 ml) were injected into the vitreous cavity via the pars plana. The animals were followed up for 1 month and then made out of the experiment. The eyes were enucleated and fixed in 10% neutral buffered formalin for routine histological examination...
2017: Vestnik Oftalmologii
Emily Welby, Jorn Lakowski, Valentina Di Foggia, Dimitri Budinger, Anai Gonzalez-Cordero, Aaron T L Lun, Michael Epstein, Aara Patel, Elisa Cuevas, Kamil Kruczek, Arifa Naeem, Federico Minneci, Mike Hubank, David T Jones, John C Marioni, Robin R Ali, Jane C Sowden
Loss of cone photoreceptors, crucial for daylight vision, has the greatest impact on sight in retinal degeneration. Transplantation of stem cell-derived L/M-opsin cones, which form 90% of the human cone population, could provide a feasible therapy to restore vision. However, transcriptomic similarities between fetal and stem cell-derived cones remain to be defined, in addition to development of cone cell purification strategies. Here, we report an analysis of the human L/M-opsin cone photoreceptor transcriptome using an AAV2/9...
November 14, 2017: Stem Cell Reports
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