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https://www.readbyqxmd.com/read/30050918/stem-cell-ophthalmology-treatment-study-bone-marrow-derived-stem-cells-in-the-treatment-of-retinitis-pigmentosa
#1
Jeffrey N Weiss, Steven Levy
Background: Seventeen patients with bilateral visual loss due to Retinitis Pigmentosa (RP) underwent autologous bone marrow derived stem cell (BMSC) treatment within the Stem Cell Ophthalmology Treatment Study (SCOTS and SCOTS 2). Both are National Institutes of Health (NIH) and Office of Human Research Protection (OHRP) compliant Institutional Review Board (IRB) approved clinical studies utilizing using autologous BMSC in the treatment of retinal and optic nerve diseases that meet inclusion criteria...
2018: Stem Cell Investigation
https://www.readbyqxmd.com/read/30026694/igf-1-inflammation-and-retinal-degeneration-a-close-network
#2
REVIEW
Ana I Arroba, Antonio Campos-Caro, Manuel Aguilar-Diosdado, Ángela M Valverde
Retinal degenerative diseases are a group of heterogeneous diseases that include age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). The progressive degeneration of the retinal neurons results in a severe deterioration of the visual function. Neuroinflammation is an early hallmark of many neurodegenerative disorders of the retina including AMD, RP and DR. Microglial cells, key components of the retinal immune defense system, are activated in retinal degenerative diseases...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29866771/plasma-exosomes-contribute-to-microvascular-damage-in-diabetic-retinopathy-by-activating-the-classical-complement-pathway
#3
Chao Huang, Kiera P Fisher, Sandra S Hammer, Svetlana Navitskaya, Gary J Blanchard, Julia V Busik
Diabetic retinopathy (DR) is a microvascular complication of diabetes and is the leading cause of vision loss in working-age adults. Recent studies have implicated the complement system as a player in the development of vascular damage and progression of DR. However, the role and activation of the complement system in DR are not well understood. Exosomes, small vesicles that are secreted into the extracellular environment, have a cargo of complement proteins in plasma, suggesting that they can participate in causing the vascular damage associated with DR...
August 2018: Diabetes
https://www.readbyqxmd.com/read/29774506/therapeutic-potential-of-mesenchymal-stem-cell-derived-exosomes-in-the-treatment-of-eye-diseases
#4
C Randall Harrell, Bojana Simovic Markovic, Crissy Fellabaum, Aleksandar Arsenijevic, Valentin Djonov, Nebojsa Arsenijevic, Vladislav Volarevic
Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases...
May 18, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29774170/liquid-biopsy-of-vitreous-reveals-an-abundant-vesicle-population-consistent-with-the-size-and-morphology-of-exosomes
#5
Yuanjun Zhao, Sarah R Weber, Joshua Lease, Mariano Russo, Christopher A Siedlecki, Li-Chong Xu, Han Chen, Weiwei Wang, Michael Ford, Rafael Simó, Jeffrey M Sundstrom
Purpose: To investigate the molecular components of the vitreous in order to better understand retinal physiology and disease. Methods: Vitreous was acquired from patients undergoing vitrectomy for macular hole and/or epiretinal membrane, postmortem donors, and C57BL/6J mice. Unbiased proteomic analysis was performed via electrospray ionization tandem mass spectrometry (MS/MS). Gene ontology analysis was performed and results were confirmed with transmission electron microscopy, atomic force microscopy, and nanoparticle tracking analysis (NTA)...
May 2018: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/29721985/polarized-exosome-release-from-the-retinal-pigmented-epithelium
#6
Mikael Klingeborn, W Daniel Stamer, Catherine Bowes Rickman
The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier and provides nutrients and recycling of visual pigment to the photoreceptors, among many other functions. The RPE is also a key site of pathophysiological changes in age-related macular degeneration, making it an important focus of study in both visual health and disease. Exosomes are nanometer-sized vesicles that are released by cells in a controlled fashion and mediate a range of extra- and intercellular activities. Some key exosome actions include cell-cell communication, immune modulation, extracellular matrix turnover, stem cell division/differentiation, neovascularization, and cellular waste removal...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29675371/mesenchymal-stem-cells-derived-exosomes-ameliorate-blue-light-stimulation-in-retinal-pigment-epithelium-cells-and-retinal-laser-injury-by-vegf-dependent-mechanism
#7
Guang-Hui He, Wei Zhang, Ying-Xue Ma, Jing Yang, Li Chen, Jian Song, Song Chen
AIM: To observe the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells (hUCMSCs) on the expression of vascular endothelial growth factor-A (VEGF-A) in blue light injured human retinal pigment epithelial (RPE) cells and laser-induced choroidal neovascularization (CNV) in rats. METHODS: Exosomes were isolated from hUCMSCs and characterized by transmission electron microscope and Western blot. MSCs-derived exosomes were cultured with RPE cells exposed to blue light...
2018: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29560091/epigenetic-modifications-in-hyperhomocysteinemia-potential-role-in-diabetic-retinopathy-and-age-related-macular-degeneration
#8
Khaled Elmasry, Riyaz Mohamed, Isha Sharma, Nehal M Elsherbiny, Yutao Liu, Mohamed Al-Shabrawey, Amany Tawfik
To study Hyperhomocysteinemia (HHcy)-induced epigenetic modifications as potential mechanisms of blood retinal barrier (BRB) dysfunction, retinas isolated from three- week-old mice with elevated level of Homocysteine (Hcy) due to lack of the enzyme cystathionine β-synthase ( cbs-/- , cbs+/- and cbs+/+ ), human retinal endothelial cells (HRECs), and human retinal pigmented epithelial cells (ARPE-19) treated with or without Hcy were evaluated for (1) histone deacetylases (HDAC), (2) DNA methylation (DNMT), and (3) miRNA analysis...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29557366/retinal-ganglion-cell-neuroprotection-by-growth-factors-and-exosomes-lessons-from-mesenchymal-stem-cells
#9
Ben Mead, Stanislav Tomarev
No abstract text is available yet for this article.
February 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29538408/human-embryonic-stem-cells-extracellular-vesicles-and-their-effects-on-immortalized-human-retinal-m%C3%A3-ller-cells
#10
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
https://www.readbyqxmd.com/read/29288268/identification-and-characterization-of-circular-rnas-as-a-new-class-of-putative-biomarkers-in-diabetes-retinopathy
#11
Shu-Jie Zhang, Xue Chen, Chao-Peng Li, Xiu-Miao Li, Chang Liu, Bai-Hui Liu, Kun Shan, Qin Jiang, Chen Zhao, Biao Yan
Purpose: To reveal the expression profile and clinical significance of circular RNAs (circRNAs) in diabetic retinopathy (DR). Methods: Circular RNA microarrays were performed to identify DR-related circRNAs. Gene ontology (GO) enrichment and KEGG analysis was performed to determine the biologic modules and signaling pathway. TargetScan and miRana program was used to predict circRNA/miRNA interaction. Quantitative PCR assays were performed to detect circRNA expression pattern in clinical samples...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29093021/the-rna-exosome-and-rna-exosome-linked-disease
#12
REVIEW
Derrick J Morton, Emily G Kuiper, Stephanie K Jones, Sara W Leung, Anita H Corbett, Milo B Fasken
The RNA exosome is an evolutionarily conserved, ribonuclease complex that is critical for both processing and degradation of a variety of RNAs. Cofactors that associate with the RNA exosome likely dictate substrate specificity for this complex. Recently, mutations in genes encoding both structural subunits of the RNA exosome and its cofactors have been linked to human disease. Mutations in the RNA exosome genes EXOSC3 and EXOSC8 cause pontocerebellar hypoplasia type 1b (PCH1b) and type 1c (PCH1c), respectively, which are similar autosomal-recessive, neurodegenerative diseases...
February 2018: RNA
https://www.readbyqxmd.com/read/28993630/%C3%AE-synuclein-impairs-ferritinophagy-in-the-retinal-pigment-epithelium-implications-for-retinal-iron-dyshomeostasis-in-parkinson-s-disease
#13
Shounak Baksi, Neena Singh
Retinal degeneration is prominent in Parkinson's disease (PD), a neuromotor disorder associated with aggregation of α-synuclein (α-syn) in the substantia-nigra (SN). Although α-syn is expressed in the neuroretina, absence of prominent aggregates suggests altered function as the likely cause of retinal pathology. We demonstrate that α-syn impairs ferritinophagy, resulting in the accumulation of iron-rich ferritin in the outer retina in-vivo and retinal-pigment-epithelial (RPE) cells in-vitro. Over-expression of Rab1a restores ferritinophagy, suggesting that α-syn impairs lysosomal function by disrupting the trafficking of lysosomal hydrolases...
October 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687758/directional-exosome-proteomes-reflect-polarity-specific-functions-in-retinal-pigmented-epithelium-monolayers
#14
Mikael Klingeborn, W Michael Dismuke, Nikolai P Skiba, Una Kelly, W Daniel Stamer, Catherine Bowes Rickman
The retinal pigmented epithelium (RPE) forms the outer blood-retinal barrier in the eye and its polarity is responsible for directional secretion and uptake of proteins, lipoprotein particles and extracellular vesicles (EVs). Such a secretional division dictates directed interactions between the systemic circulation (basolateral) and the retina (apical). Our goal is to define the polarized proteomes and physical characteristics of EVs released from the RPE. Primary cultures of porcine RPE cells were differentiated into polarized RPE monolayers on permeable supports...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28636406/protective-effect-of-intravitreal-administration-of-exosomes-derived-from-mesenchymal-stem-cells-on-retinal-ischemia
#15
Elad Moisseiev, Johnathon D Anderson, Sharon Oltjen, Mayank Goswami, Robert J Zawadzki, Jan A Nolta, Susanna S Park
PURPOSE: Exosomes derived from human mesenchymal stem cells (hMSCs) cultured under hypoxic conditions contain proteins and growth factors that promote angiogenesis. This study investigated the effect of intravitreal administration of these exosomes on retinal ischemia using a murine model. METHODS: Oxygen-induced retinopathy (OIR) was induced by exposing one-week-old male C57BL/6J mice to 5 days of 75% hyperoxic conditioning, and returning to room air. After hyperoxic conditioning, the right eye of each mouse was injected intravitreally with 1 µl saline or exosomes derived from hMSCs and compared to control mice of the same age raised in room air without OIR injected intravitreally with saline...
October 2017: Current Eye Research
https://www.readbyqxmd.com/read/28361998/exosome-associated-aav2-vector-mediates-robust-gene-delivery-into-the-murine-retina-upon-intravitreal-injection
#16
Sarah J Wassmer, Livia S Carvalho, Bence György, Luk H Vandenberghe, Casey A Maguire
Widespread gene transfer to the retina is challenging as it requires vector systems to overcome physical and biochemical barriers to enter and diffuse throughout retinal tissue. We investigated whether exosome-associated adeno-associated virus, (exo-AAV) enabled broad retinal targeting following intravitreal (IVT) injection, as exosomes have been shown to traverse biological barriers and mediate widespread distribution upon systemic injection. We packaged an AAV genome encoding green fluorescent protein (GFP) into conventional AAV2 and exo-AAV2 vectors...
March 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198592/bone-marrow-derived-mesenchymal-stem-cells-derived-exosomes-promote-survival-of-retinal-ganglion-cells-through-mirna-dependent-mechanisms
#17
Ben Mead, Stanislav Tomarev
The loss of retinal ganglion cells (RGC) and their axons is one of the leading causes of blindness and includes traumatic (optic neuropathy) and degenerative (glaucoma) eye diseases. Although no clinical therapies are in use, mesenchymal stem cells (MSC) have demonstrated significant neuroprotective and axogenic effects on RGC in both of the aforementioned models. Recent evidence has shown that MSC secrete exosomes, membrane enclosed vesicles (30-100 nm) containing proteins, mRNA and miRNA which can be delivered to nearby cells...
April 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28173719/exosomal-microrna-15a-transfer-from-the-pancreas-augments-diabetic-complications-by-inducing-oxidative-stress
#18
Tengku Ain Kamalden, Anne M Macgregor-Das, Sangeetha Marimuthu Kannan, Brittany Dunkerly-Eyring, Nurliza Khaliddin, Zhenhua Xu, Anthony P Fusco, Syatirah Abu Yazib, Rhuen Chiou Chow, Elia J Duh, Marc K Halushka, Charles Steenbergen, Samarjit Das
AIMS: MicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D. RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic β-cells...
November 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28082074/rescue-of-hearing-by-gene-delivery-to-inner-ear-hair-cells-using-exosome-associated-aav
#19
Bence György, Cyrille Sage, Artur A Indzhykulian, Deborah I Scheffer, Alain R Brisson, Sisareuth Tan, Xudong Wu, Adrienn Volak, Dakai Mu, Panos I Tamvakologos, Yaqiao Li, Zachary Fitzpatrick, Maria Ericsson, Xandra O Breakefield, David P Corey, Casey A Maguire
Adeno-associated virus (AAV) is a safe and effective vector for gene therapy for retinal disorders. Gene therapy for hearing disorders is not as advanced, in part because gene delivery to sensory hair cells of the inner ear is inefficient. Although AAV transduces the inner hair cells of the mouse cochlea, outer hair cells remain refractory to transduction. Here, we demonstrate that a vector, exosome-associated AAV (exo-AAV), is a potent carrier of transgenes to all inner ear hair cells. Exo-AAV1-GFP is more efficient than conventional AAV1-GFP, both in mouse cochlear explants in vitro and with direct cochlear injection in vivo...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/27876140/retinal-pigment-epithelium-cell-derived-exosomes-possible-relevance-to-cnv-in-wet-age-related-macular-degeneration
#20
Yao Tong, Ya-Li Zhou, Yi-Xiao Wang, Pei-Quan Zhao, Zhao-Yang Wang
Exosomes are small vesicles that are released by almost every cell type and play a crucial role in many physiological and pathological processes associated with different diseases. Specifically, they promote angiogenesis in the pathogenesis of some diseases. According to previous research, the proteins of exosomes taken from the aqueous humor (AH) of patients with wet-age related macular degeneration (AMD) may function as a new diagnostic biomarker of AMD, suggesting that exosomes may play an important role in the occurrence and development of choroidal neovascularization (CNV)...
December 2016: Medical Hypotheses
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