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https://www.readbyqxmd.com/read/28632880/the-urokinase-receptor-derived-peptide-uparant-recovers-dysfunctional-electroretinogram-and-blood-retinal-barrier-leakage-in-a-rat-model-of-diabetes
#1
Maurizio Cammalleri, Filippo Locri, Stefania Marsili, Massimo Dal Monte, Claudio Pisano, Angelo Mancinelli, Liliana Lista, Dario Rusciano, Mario De Rosa, Vincenzo Pavone, Paola Bagnoli
Purpose: The activation of the urokinase-type plasminogen activator and its receptor system is associated with retinal diseases. Among peptide inhibitors of this system, UPARANT acts by preventing the onset of pathologic signs of neovascular ocular diseases. We investigated whether systemic UPARANT may act in a therapeutic regimen by suppressing the retinal damage that characterizes diabetic retinopathy using a rat model of streptozotocin-induced diabetes. Methods: In healthy rats, plasma, eye, and retina concentrations of UPARANT were evaluated by mass spectrometry...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28632458/aquaporins-novel-targets-for-age-related-ocular-disorders
#2
Rajkumar Patil, Haishan Wang, Najam A Sharif, Alok Mitra
Aquaporins (AQPs), a large family of membrane protein channels that facilitate transport of water and other small solutes, play important roles in physiological functions and human diseases. Up till now, 13 types of AQPs, numbered 0 through 12, have been identified in various mammalian tissues. Homologous genes for AQPs in amphibians, insects, and bacteria highlight the evolutionary conservation and, thus, the importance of these membrane channels. Many members of the AQP family are expressed in the eye. AQP1, which is a water-selective channel, is expressed in the anterior chamber (cornea, ciliary body, trabecular meshwork) and posterior chamber (retina and microvessels in choroid), controlling the fluid homeostasis in the eye...
June 20, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28631245/hypoxia-and-inflammation-in-the-release-of-vegf-and-interleukins-from-human-retinal-pigment-epithelial-cells
#3
Olli Arjamaa, Vesa Aaltonen, Niina Piippo, Tamás Csont, Goran Petrovski, Kai Kaarniranta, Anu Kauppinen
PURPOSE: Retinal diseases are closely associated with both decreased oxygenation and increased inflammation. It is not known if hypoxia-induced vascular endothelial growth factor (VEGF) expression in the retina itself evokes inflammation, or whether inflammation is a prerequisite for the development of neovascularization. METHODS: Human ARPE-19 cell line and primary human retinal pigment epithelium (RPE) cells were used. ARPE-19 cells were kept either under normoxic (24 h or 48 h) or hypoxic conditions (1% O2, 24 h)...
June 19, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28629927/quick-freeze-deep-etch-electron-microscopy-visualization-of-the-mouse-posterior-pole
#4
Ebraheim N Ismail, Jeffrey W Ruberti, Goldis Malek
The mouse is one of the most commonly used mammalian systems to study human diseases. In particular it has been an invaluable tool to model a multitude of ocular pathologies affecting the posterior pole. The aim of this study was to create a comprehensive map of the ultrastructure of the mouse posterior pole using the quick-freeze/deep-etch method (QFDE). QFDE can produce detailed three-dimensional images of tissue structure and macromolecular moieties, without many of the artifacts introduced by structure-altering post-processing methods necessary to perform conventional transmission electron microscopy (cTEM)...
June 16, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28629380/retinal-and-vitreous-metastases-from-hepatocholangiocarcinoma
#5
Anna Praidou, Sarita Jacob, Luciane Irion, Ramesh Sivaraj, Carl Groenewald, Sarah E Coupland, Heinrich Heimann
BACKGROUND: To report a case of metastatic hepatocholangiocarcinoma to the vitreous and retina. CASE PRESENTATION: A 70-year-old male, who was recently diagnosed with hepatocholangiocarcinoma, was complaining of floaters in his right eye over the past 5 months and was referred to the Liverpool Ocular Oncology Centre. On presentation, his visual acuity in the right eye was 6/24. Fundus exam revealed a whitish, unilateral, full-thickness retinal lesion at the inferotemporal arcade of his right eye, with vitreous infiltration and subretinal fluid...
June 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28627621/identification-of-different-macrophage-subpopulations-with-distinct-activities-in-a-mouse-model-of-oxygen-induced-retinopathy
#6
Yanji Zhu, Ling Zhang, Qing Lu, Yushuo Gao, Yujuan Cai, Ailing Sui, Ting Su, Xi Shen, Bing Xie
The aim of the present study was to characterize the phenotypic shift, quantity and role changes in different subgroups of retinal macrophages in a mouse model of oxygen-induced retinopathy (OIR). The mRNA expression levels of macrophage M1 and M2 subgroup marker genes and polarization-associated genes were analyzed by RT-qPCR. The number of M1 and M2 macrophages in our mouse model of OIR was analyzed by flow cytometry at different time points during the progression of OIR. Immunofluorescence whole mount staining of the retinas of mice with OIR was performed at different time points to examine the influx of macrophages, as well as the morphological characteristics and roles of M1 and M2 macrophages...
June 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28626601/long-term-efficacy-of-gmp-grade-xeno-free-hesc-derived-rpe-cells-following-transplantation
#7
Trevor J McGill, Osnat Bohana-Kashtan, Jonathan W Stoddard, Michael D Andrews, Neelay Pandit, Lior R Rosenberg-Belmaker, Ofer Wiser, Limor Matzrafi, Eyal Banin, Benjamin Reubinoff, Nir Netzer, Charles Irving
PURPOSE: Retinal pigment epithelium (RPE) dysfunction underlies the retinal degenerative process in age-related macular degeneration (AMD), and thus RPE cell replacement provides an optimal treatment target. We characterized longitudinally the efficacy of RPE cells derived under xeno-free conditions from clinical and xeno-free grade human embryonic stem cells (OpRegen) following transplantation into the subretinal space of Royal College of Surgeons (RCS) rats. METHODS: Postnatal (P) day 20 to 25 RCS rats (n = 242) received a single subretinal injection of 25,000 (low)-, 100,000 (mid)-, or 200,000 (high)-dose xeno-free RPE cells...
June 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28626250/association-between-changes-in-visual-evoked-magnetic-fields-and-non-motor-features-in-parkinson-s-disease
#8
Yoshiro Fujisawa, Tomomi Minato, Jun-Ichi Uemura, Minoru Hoshiyama, Hirohisa Watanabe, Masaaki Hirayama
Visual dysfunction can be caused by several abnormalities, including dysfunctions in the visual cortex and retina. Our aim was to investigate changes in visual evoked brain responses in the primary visual cortex associated with Parkinson's disease (PD). Sixteen healthy control subjects and ten patients with PD participated in this study. We assessed the visual evoked magnetic field (VEF) using magnetoencephalography (MEG). Checkerboard pattern reversal (CPR) and monotonous grating pattern (MGP) stimulations were used...
February 2017: Nagoya Journal of Medical Science
https://www.readbyqxmd.com/read/28625845/injury-and-defective-regeneration-of-the-epithelial-basement-membrane-in-corneal-fibrosis-a-paradigm-for-fibrosis-in-other-organs
#9
REVIEW
Steven E Wilson, Gustavo K Marino, Andre A M Torricelli, Carla S Medeiros
Myofibroblast-mediated fibrosis is important in the pathophysiology of diseases in most organs. The cornea, the transparent anterior wall of the eye that functions to focus light on the retina, is commonly affected by fibrosis and provides an optimal model due to its simplicity and accessibility. Severe injuries to the cornea, including infection, surgery, and trauma, may trigger the development of myofibroblasts and fibrosis in the normally transparent connective tissue stroma. Ultrastructural studies have demonstrated that defective epithelial basement membrane (EBM) regeneration after injury underlies the development of myofibroblasts from both bone marrow- and keratocyte-derived precursor cells in the cornea...
June 15, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28623239/-ccug-n-rna-toxicity-in-a-drosophila-model-for-myotonic-dystrophy-type-2-dm2-activates-apoptosis
#10
Vildan Betul Yenigun, Mario Sirito, Alla Amcheslavky, Tomek Czernuszewicz, Jordi Colonques-Bellmunt, Irma García-Alcover, Marzena Wojciechowska, Clare Bolduc, Zhihong Chen, Arturo López Castel, Ralf Krahe, Andreas Bergmann
The myotonic dystrophies are prototypic toxic RNA gain-of-function diseases. Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are caused by different unstable, noncoding microsatellite repeat expansions -- (CTG)DM1 in DMPK and (CCTG)DM2 in CNBP Although transcription of mutant repeats into (CUG)DM1 or (CCUG)DM2 appears to be necessary and sufficient to cause disease, their pathomechanisms remain incompletely understood. To study the mechanisms of (CCUG)DM2 toxicity and develop a convenient model for drug screening, we generated a transgenic DM2 model in the fruit fly Drosophila melanogaster with (CCUG)n repeats of variable length (n=16 and 106)...
June 16, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28619647/using-crispr-cas9-to-generate-gene-corrected-autologous-ipscs-for-the-treatment-of-inherited-retinal-degeneration
#11
Erin R Burnight, Manav Gupta, Luke A Wiley, Kristin R Anfinson, Audrey Tran, Robinson Triboulet, Jeremy M Hoffmann, Darcey L Klaahsen, Jeaneen L Andorf, Chunhua Jiao, Elliott H Sohn, Malavika K Adur, Jason W Ross, Robert F Mullins, George Q Daley, Thorsten M Schlaeger, Edwin M Stone, Budd A Tucker
Patient-derived induced pluripotent stem cells (iPSCs) hold great promise for autologous cell replacement. However, for many inherited diseases, treatment will likely require genetic repair pre-transplantation. Genome editing technologies are useful for this application. The purpose of this study was to develop CRISPR-Cas9-mediated genome editing strategies to target and correct the three most common types of disease-causing variants in patient-derived iPSCs: (1) exonic, (2) deep intronic, and (3) dominant gain of function...
June 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28617420/mirna-mediated-post-transcriptional-silencing-of-transgenes-leads-to-increased-adeno-associated-viral-vector-yield-and-targeting-specificity
#12
C A Reid, S L Boye, W W Hauswirth, D M Lipinski
The production of high titer recombinant adeno-associated virus (rAAV) vector is essential for treatment of genetic diseases affecting the retina and choroid, where anatomical constraints may limit injectable volumes. Problematically, cytotoxicity arising from over-expression of the transgene during vector production frequently leads to a reduction in vector yield. Herein, we evaluate the use of micro-RNA (miRNA) mediated silencing to limit over-expression of cytotoxic transgenes during packaging as a method of increasing vector yield...
June 15, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28616257/book-review-spectral-domain-optical-coherence-tomography-in-macular-diseases
#13
Müller Gonçalves Urias, Eduardo Büchele Rodrigues
This is a review of the book Spectral Domain Optical Coherence Tomography in Macular Diseases edited by Meyer et al. (Spectral domain optical coherence tomography in macular diseases. Springer, New York, [2017]). The book provides clinicians both basic and advanced understanding of OCT applications in the field of medical retina.
2017: International Journal of Retina and Vitreous
https://www.readbyqxmd.com/read/28615447/human-retinal-pigment-epithelium-cells-prefer-proline-as-a-nutrient-and-transport-metabolic-intermediates-to-the-retinal-side
#14
Jennifer R Chao, Kaitlen Knight, Abbi L Engel, Connor Jankowski, Yekai Wang, Megan A Manson, Haiwei Gu, Danijel Djukovic, Daniel Raftery, James B Hurley, Jianhai Du
Metabolite transport is a major function for the retinal pigment epithelium (RPE) to support the neural retina. RPE dysfunction plays a significant role in retinal degenerative diseases. We have used mass spectrometry with (13)C tracers to systematically study nutrient consumption and metabolite transport in cultured human fetal RPE. LC MS/MS detected 120 metabolites in the medium from either the apical or basal side. Surprisingly, more proline is consumed than any other nutrient including glucose, taurine, lipids, vitamins, or other amino acids...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28614042/bnip3l-nix-dependent-mitophagy-regulates-cell-differentiation-via-metabolic-reprogramming
#15
Lorena Esteban-Martínez, Patricia Boya
Macroautophagy/autophagy is the process by which cellular components are degraded and recycled within the lysosome. These components include mitochondria, the selective degradation of which is known as mitophagy. Mitochondria are dynamic organelles that constantly adapt their morphology, function, and number to accommodate the metabolic needs of the cell. Extensive metabolic reconfiguration occurs during cell differentiation, when mitochondrial activity increases in most cell types. However, our data demonstrate that during physiological retinal ganglion cell (RGC) development, mitophagy-dependent metabolic reprogramming towards glycolysis regulates numbers of RGCs, which are the first neurons to differentiate in the retina and whose axons form the optic nerve...
June 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28613354/the-quantitative-measurements-of-vascular-density-and-flow-areas-of-macula-using-optical-coherence-tomography-angiography-in-normal-volunteers
#16
Fariba Ghassemi, Kaveh Fadakar, Fatemeh Bazvand, Reza Mirshahi, Masoumeh Mohebbi, Siamak Sabour
BACKGROUND AND OBJECTIVE: The quantification of the density of macular vascular networks and blood flow areas in the foveal and parafoveal area in healthy subjects using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: Cross-sectional, prospective study in an institutional setting at the Retina Services of Farabi Eye Hospital. One hundred twelve normal volunteers with no known ocular or systemic disease were included, including patient numbers (one or both eyes), selection procedures, inclusion/exclusion criteria, randomization procedure, and masking...
June 1, 2017: Ophthalmic Surgery, Lasers & Imaging Retina
https://www.readbyqxmd.com/read/28612282/probing-of-peripheral-blood-mononuclear-cells-anchoring-on-tnf-alpha-challenged-vascular-endothelia-in-an-in-vitro-model-of-the-retinal-microvascular
#17
Yuan Li, Yao Lu, Qiong Chen, Yuejun Kang, Ling Yu
Retinopathy is a complication of diabetes that affects the eyes; it stems from damage to the microvasculature of the retina and eventually compromises vision. The diagnosis of retinopathy is difficult to make because there are no early symptoms or warning signs. Dysfunction of the retina's microvascular networks is believed to be associated with inflammatory cytokines and tumor necrosis factor alpha (TNF-α). To investigate the effect of these cytokines, such as TNF-α, a polydimethylsiloxane (PDMS)/glass hydride microfluidic device reflecting the physiological structure of the retina's microvasculature was developed...
September 2017: Biomedical Microdevices
https://www.readbyqxmd.com/read/28604388/targeting-neuronal-gap-junctions-in-mouse-retina-offers-neuroprotection-in-glaucoma
#18
Abram Akopian, Sandeep Kumar, Hariharasubramanian Ramakrishnan, Kaushambi Roy, Suresh Viswanathan, Stewart A Bloomfield
The progressive death of retinal ganglion cells and resulting visual deficits are hallmarks of glaucoma, but the underlying mechanisms remain unclear. In many neurodegenerative diseases, cell death induced by primary insult is followed by a wave of secondary loss. Gap junctions (GJs), intercellular channels composed of subunit connexins, can play a major role in secondary cell death by forming conduits through which toxic molecules from dying cells pass to and injure coupled neighbors. Here we have shown that pharmacological blockade of GJs or genetic ablation of connexin 36 (Cx36) subunits, which are highly expressed by retinal neurons, markedly reduced loss of neurons and optic nerve axons in a mouse model of glaucoma...
June 12, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28602949/connexin-channel-and-its-role-in-diabetic-retinopathy
#19
REVIEW
Sayon Roy, Jean X Jiang, An-Fei Li, Dongjoon Kim
Diabetic retinopathy is the leading cause of blindness in the working age population. Unfortunately, there is no cure for this devastating ocular complication. The early stage of diabetic retinopathy is characterized by the loss of various cell types in the retina, namely endothelial cells and pericytes. As the disease progresses, vascular leakage, a clinical hallmark of diabetic retinopathy, becomes evident and may eventually lead to diabetic macular edema, the most common cause of vision loss in diabetic retinopathy...
June 7, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28602870/ultrasound-mediated-nanoparticle-delivery-across-ex-vivo-bovine-retina-after-intravitreal-injection
#20
Di Huang, Ying-Shan Chen, Ilva D Rupenthal
Intravitreal injection is the most common administration route for the treatment of retinal diseases. However, the vitreous and some of the retinal layers themselves act as significant barriers to efficient delivery of drugs administered intravitreally. This study aimed to improve the diffusive mobility of nanoparticles (NPs) in the vitreous and enhance their permeation across the retina after intravitreal injection by application of ultrasound (US). Ex vivo posterior bovine eye cups were used and the vitreous was either left intact or removed gently from the neural retina...
June 8, 2017: European Journal of Pharmaceutics and Biopharmaceutics
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